Hemodialysis systems and methods

ABSTRACT

Disclosed are hemodialysis and similar dialysis systems including fluid flow circuits. Hemodialysis systems may include a blood flow path, and a dialysate flow path including balancing, mixing, and/or a directing circuits. Preparation of dialysate may be decoupled from patient dialysis. Circuits may be defined within one or more cassettes. The fluid circuit and/or the various fluid flow paths may be isolated from electrical components. A gas supply may be provided that, when activated, is able to urge dialysate through the dialyzer and blood back to the patient. Such a system may be useful during a power failure. The hemodialysis system may also include fluid handling devices, such as pumps, valves, mixers, etc., actuated using a control fluid. The control fluid may be delivered to the fluid handling devices using a detachable external pump. The fluid handling devices may have a spheroid shape with a diaphragm dividing it into two compartments.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/262,101, filed Apr. 25, 2014, and issued as U.S. Pat. No. 9,555,179on Jan. 31, 2017, which is a divisional of U.S. patent application Ser.No. 13/569,623, filed Aug. 8, 2012, and issued as U.S. Pat. No.8,721,884 on May 13, 2014 entitled, “Hemodialysis Systems and Methods,”which is a divisional of U.S. patent application Ser. No. 12/072,908,filed Feb. 27, 2008, and issued as U.S. Pat. No. 8,246,826 on Aug. 21,2012, entitled “Hemodialysis Systems and Methods,” which claims thebenefit of U.S. Provisional Patent Application Ser. No. 60/903,582,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods,” andU.S. Provisional Patent Application Ser. No. 60/904,024, filed Feb. 27,2007, entitled “Hemodialysis System and Methods.” Each of these isincorporated herein by reference.

FIELD OF INVENTION

The present invention generally relates to hemodialysis and similardialysis systems, e.g., systems able to treat blood or other bodilyfluids extracorporeally. In certain aspects, the systems include avariety of systems and methods that would make hemodialysis moreefficient, easier, and/or more affordable.

BACKGROUND

Many factors make hemodialysis inefficient, difficult, and expensive.These factors include the complexity of hemodialysis, the safetyconcerns related to hemodialysis, and the very large amount of dialysateneeded for hemodialysis. Moreover, hemodialysis is typically performedin a dialysis center requiring skilled technicians. Therefore anyincrease in the ease and efficiency of the dialysis process could havean impact on treatment cost or patient outcome.

FIG. 1 is a schematic representation of a hemodialysis system. Thesystem 5 includes two flow paths, a blood flow path 10 and a dialysateflow path 20. Blood is drawn from a patient. A blood flow pump 13 causesthe blood to flow around blood flow path 10, drawing the blood from thepatient, causing the blood to pass through the dialyzer 14, andreturning the blood to the patient. Optionally, the blood may passthrough other components, such as a filter and/or an air trap 19, beforereturning to the patient. In addition, in some cases, anticoagulant maybe supplied from an anticoagulant supply 11 via an anticoagulant valve12.

A dialysate pump 15 draws dialysate from a dialysate supply 16 andcauses the dialysate to pass through the dialyzer 14, after which thedialysate can pass through a waste valve 18 and/or return to thedialysate feed via dialysate pump 15. A dialysate valve 17 controls theflow of dialysate from the dialysate supply 16. The dialyzer isconstructed such that the blood from the blood flow circuit flowsthrough tiny tubes and the dialysate solution circulates around theoutside of the tubes. Therapy is achieved by the passing of wastemolecules (e.g., urea, creatinine, etc.) and water from the bloodthrough the walls of the tubes and into the dialysate solution. At theend of treatment, the dialysate solution is discarded.

SUMMARY OF THE INVENTION

The present invention generally relates to hemodialysis and similardialysis systems. The subject matter of the present invention involves,in some cases, interrelated products, alternative solutions to aparticular problem, and/or a plurality of different uses of one or moresystems and/or articles. Although the various systems and methodsdescribed herein are described in relation to hemodialysis, it should beunderstood that the various systems and method described herein areapplicable to other dialysis systems and/or in any extracorporeal systemable to treat blood or other bodily fluids, such as hemofiltration,hemodiafiltration, etc.

In one aspect, the system includes four fluid paths: blood; innerdialysate; outer dialysate and dialysate mixing. In some embodiments,these four paths are combined in a single cassette. In otherembodiments, these four paths are each in a respective cassette. Instill other embodiments, two or more fluid paths are included on onecassette.

In one embodiment, there is provided a hemodialysis system having atleast two fluid paths integrated into: 1) a blood flow pump cassette, 2)an inner dialysate cassette; 3) an outer dialysate cassette; and 4) amixing cassette. The cassettes may be fluidly connected one to another.In some embodiments, one or more aspects of these cassettes can becombined into a single cassette.

Also provided, in another embodiment, is a hemodialysis system includinga blood flow path through which untreated blood is drawn from a patientand is passed through a dialyzer and through which treated blood isreturned to the patient. The blood flow path may include at least oneblood flow pump located in a removable cassette. The hemodialysis systemalso can include a first receiving structure for receiving the bloodflow path's cassette, a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer, a second receivingstructure for receiving the dialysate flow path's cassette, and acontrol fluid path for providing a control fluid from an actuatormechanism to the cassettes for actuating each of the blood flow pump andthe dialysate pump. In some instances, the dialysate flow path caninclude at least one dialysate pump located in a removable cassette.

In yet another embodiment, a hemodialysis system is disclosed. Thehemodialysis system, in this embodiment, includes a blood flow paththrough which untreated blood is drawn from a patient and is passedthrough a dialyzer and through which treated blood is returned to thepatient. The blood flow path may include at least one blood valve. Thehemodialysis system may also include a control fluid path for providinga control fluid from an actuator mechanism to the blood valve foractuating the blood valve, a dialysate mixing system fluidly connectedto the dialyzer (which may include at least one dialyzer valve), and aheating means or a heater for heating the dialysate.

A hemodialysis system is disclosed in yet another embodiment thatincludes a blood flow path through which untreated blood is drawn from apatient and passed through a dialyzer and through which treated blood isreturned to the patient. The blood flow path can include at least oneblood flow pump. The hemodialysis system also can include a dialysateflow path through which dialysate flows from a dialysate supply throughthe dialyzer. The dialysate flow path may include at least one pneumaticpump.

In one aspect, the invention is directed to a hemodialysis system. Inone set of embodiments, the hemodialysis system includes a blood flowpath, a first cassette defining an inner dialysate fluid path, adialyzer in fluid communication with the blood flow path and the innerdialysate fluid path, a second cassette defining an outer dialysatefluid path, and a filter fluidly connecting the first cassette to thesecond cassette.

In another set of embodiments, the hemodialysis system, includes a bloodflow path, an inner dialysate fluid path, a dialyzer in fluidcommunication with the blood flow path and the inner dialysate fluidpath, an outer dialysate fluid path, a filter fluidly connecting theinner dialysate fluid path and the outer dialysate fluid path, a firstdialysate pump for pumping dialysate through the inner dialysate fluidpath, and a second dialysate pump for pumping dialysate through theouter dialysate fluid path, where the second dialysate pump and thefirst dialysate pump are operably connected such that flow through theinner dialysate fluid path is substantially equal to flow through theouter dialysate fluid path.

The hemodialysis system, in yet another set of embodiments, includes ablood flow path through which blood is drawn from a patient and passedthrough a dialyzer, and a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer. In some cases, thedialysate flow path comprises a balancing cassette which controls theamount of dialysate passing through the dialyzer, a mixing cassettewhich forms dialysate from water, and a directing cassette which passeswater from a water supply to the mixing cassette and passes dialysatefrom the mixing cassette to the balancing cassette.

In still another set of embodiments, the hemodialysis system includes acassette system, comprising a directing cassette, a mixing cassette anda balancing cassette. In some cases, the directing cassette is able todirect water from a water supply to the mixing cassette and directdialysate from the mixing cassette to a balancing cassette, the mixingcassette is able to mix water from the directing cassette with dialysatefrom a dialysate supply precursor to produce a precursor, and thebalancing cassette is able to control the amount of dialysate passingthrough a dialyzer.

In one set of embodiments, the hemodialysis system includes a blood flowpath through which blood is drawn from a patient and passed through adialyzer, the blood flow path including a blood flow pump, a dialysateflow path through which dialysate flows from a dialysate supply throughthe dialyzer, where the dialysate flow path includes a dialysate pump,and a control fluid path through which a control fluid actuates theblood flow pump and the dialysate pump.

The hemodialysis system, in another set of embodiments, comprises ablood flow path through which blood is drawn from a patient and passedthrough a dialyzer; and a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer. In some cases, thedialysate flow path includes at least one pneumatic pump.

The hemodialysis system, in still another set of embodiments, includes afirst pump comprising a pumping chamber and an actuation chamber, asecond pump comprising a pumping chamber and an actuation chamber, acontrol fluid in fluidic communication with each of the actuationchambers of the first and second pumps, and a controller able topressurize the control fluid to control operation of the first andsecond pumps.

In yet another set of embodiments, the hemodialysis system includes afirst valve comprising a valving chamber and an actuation chamber, asecond valve comprising a valving chamber and an actuation chamber, acontrol fluid in fluidic communication with each of the actuationchambers of the first and second valves, and a controller able topressurize the control fluid to control operation of the first andsecond valves.

In one set of embodiments, the hemodialysis system includes a blood flowpath through which blood is drawn from a patient and passed through adialyzer, a cassette containing at least a portion of the blood flowpath, and a spike integrally formed with the cassette, the spike able toreceive a vial of fluid, the integrally formed spike in fluidiccommunication with the blood flow path within the cassette.

The hemodialysis system, in another set of embodiments, includes a bloodflow path through which untreated blood is drawn from a patient andpassed through a dialyzer, a dialysate flow path through which dialysateflows from a dialysate supply through the dialyzer, the dialyzerpermitting dialysate to pass from the dialysate flow path to the bloodflow path, and a gas supply in fluidic communication with the dialysateflow path so that, when activated, gas from the gas supply causes thedialysate to pass through the dialyzer and urge blood in the blood flowpath back to the patient.

In yet another set of embodiments, the hemodialysis system includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, a dialysate flow path through whichdialysate flows from a dialysate supply through the dialyzer, thedialyzer permitting dialysate to pass from the dialysate flow path tothe blood flow path, a fluid supply, a chamber in fluid communicationwith the fluid supply and the dialysate fluid path, the chamber having adiaphragm separating fluid of the fluid supply from dialysate of thedialysate flow path, and a pressurizing device for pressurizing thefluid supply to urge the diaphragm against the dialysate in the chamber,so as to cause the dialysate to pass through the dialyzer and urge bloodin the blood flow path back to the patient.

The hemodialysis system, in still another set of embodiments, includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, a dialysate flow path through whichdialysate flows from a dialysate supply through the dialyzer, thedialysate flow path and the blood flow path being in fluidiccommunication, and a pressure device able to urge dialysate in thedialysate flow path to flow into the blood flow path.

In one set of embodiments, the hemodialysis system includes a firsthousing containing a positive-displacement pump actuated by a controlfluid, a fluid conduit fluidly connecting the positive-displacement pumpwith a control fluid pump, and a second housing containing the controlfluid pump, where the second housing is detachable from the firsthousing.

In another set of embodiments, the hemodialysis system includes ahousing comprising a first compartment and a second compartmentseparated by an insulating wall, the first compartment beingsterilizable at a temperature of at least about 80° C., the secondcompartment containing electronic components that, when the firstcompartment is heated to a temperature of at least about 80° C., are notheated to a temperature of more than 60° C.

The hemodialysis system, in yet another set of embodiments, includes ablood flow path through which untreated blood is drawn from a patientand passed through a dialyzer, the blood flow path including at leastone blood valve; a control fluid path for providing a control fluid froman actuator mechanism to the blood valve for actuating the blood valve;a dialysate mixing system fluidly connected to the dialyzer, includingat least one dialyzer valve; and a heater for heating the dialysate.

Another aspect of the present invention is directed to a valving system.In one set of embodiments, the valving system includes a valve housingcontaining a plurality of valves, at least two of which valves eachcomprises a valving chamber and an actuation chamber, each of the atleast two valves being actuatable by a control fluid in the actuationchamber; a control housing having a plurality of fluid-interface portsfor providing fluid communication with a control fluid from a base unit;and a plurality of tubes extending between the valve housing and thecontrol housing, each tube providing fluid communication between one ofthe fluid-interface ports and at least one of the actuation chambers,such that the base unit can actuate a valve by pressurizing controlfluid in the fluid interface port.

In one set of embodiments, the invention is directed to a valveincluding a first plate; a second plate, the second plate having anindentation on a side facing the first plate, the indentation having agroove defined therein, the groove being open in a direction facing thefirst plate; a third plate, wherein the second plate is located betweenthe first and third plate; and a diaphragm located in the indentationbetween the first plate and the second plate, the diaphragm having arim, the rim being held in the groove. The second plate may include avalve seat arranged so that the diaphragm may be urged by pneumaticpressure to seal the valve seat closed, the groove surrounding the valveseat. In some cases, a valve inlet and a valve outlet are definedbetween the second and third plates. In one embodiment, a passage forproviding pneumatic pressure is defined between the first and secondplates.

Yet another aspect of the present invention is directed to a pumpingsystem. The pumping system, in one set of embodiments, includes a pumphousing containing a plurality of pumps, at least two of which pumpseach includes a pumping chamber and an actuation chamber, each of the atleast two pumps being actuatable by a control fluid in the actuationchamber; a control housing having a plurality of fluid-interface portsfor providing fluid communication with a control fluid from a base unit;and a plurality of tubes extending between the pump housing and thecontrol housing, each tube providing fluid communication between one ofthe fluid-interface ports and at least one of the actuation chambers,such that the base unit can actuate a pump by pressurizing control fluidin the fluid interface port.

The invention is generally directed to a pumping cassette in anotheraspect. In one set of embodiments, the pumping cassette includes atleast one fluid inlet, at least one fluid outlet, a flow path connectingthe at least one fluid inlet and the at least one fluid outlet, and aspike for attaching a vial to said cassette. The spike may be in fluidiccommunication with the flow path in some cases.

In one aspect, the invention is generally directed to a pumping cassettefor balancing flow to and from a target. In one set of embodiments, thepumping cassette includes a cassette inlet, a supply line to the target,a return line from the target, a cassette outlet, a pumping mechanismfor causing fluid to flow from the cassette inlet to the supply line andfrom the return line to the cassette outlet, and a balancing chamber. Insome cases, the pumping mechanism includes a pod pump comprising a rigidcurved wall defining a pumping volume and having an inlet and an outlet,a pump diaphragm mounted within the pumping volume; and an actuationport for connecting the pod pump to a pneumatic actuation system so thatthe diaphragm can be actuated to urge fluid into and out of the pumpingvolume, wherein the pump diaphragm separates the fluid from a gas influid communication with the pneumatic actuation system. In certaininstances, the balancing chamber includes a rigid curved wall defining abalance volume; and a balance diaphragm mounted within the balancevolume, where the balance diaphragm separates the balance volume into asupply side and a return side, each of the supply side and the returnside having an inlet and an outlet. In some cases, fluid from thecassette inlet flows to the supply side inlet, fluid from the supplyside outlet flows to the supply line, fluid from the return line flowsto the return side inlet, and fluid from the return side outlet flows tothe cassette outlet.

In another set of embodiments, the pumping system includes a systeminlet, a supply line to the target, a return line from the target, asystem outlet, a pumping mechanism for causing fluid to flow from thesystem inlet to the supply line and from the return line to the systemoutlet, and a balancing chamber.

In one embodiment, the pumping mechanism includes a pod pump comprisinga rigid spheroid wall defining a pumping volume and having an inlet andan outlet, a pump diaphragm mounted within and to the spheroid wall, anda port for connecting the pod pump to a pneumatic actuation system sothat the diaphragm can be actuated to urge fluid into and out of thepumping volume. In some cases, the pump diaphragm separates the fluidfrom a gas in fluid communication with the pneumatic actuation system;

In certain instances, the balancing chamber includes a rigid spheroidwall defining a balance volume, and a balance diaphragm mounted withinand to the spheroid wall. In one embodiment, the balance diaphragmseparates the balance volume into a supply side and a return side, eachof the supply side and the return side having an inlet and an outlet. Insome cases, fluid from the system inlet flows to the supply side inlet,fluid from the supply side outlet flows to the supply line, fluid fromthe return line flows to the return side inlet, and fluid from thereturn side outlet flows to the system outlet. The pumping mechanism mayalso include valving mechanisms located at each of the inlets andoutlets of the supply side and the return side. The valving mechanismsmay be pneumatically actuated.

Yet another aspect of the invention is directed to a cassette. In oneset of embodiments, the cassette includes a first flow path connecting afirst inlet to a first outlet, a second flow path connecting a secondinlet to a second outlet, a pump able to pump fluid through at least aportion of the second flow path, and at least two balancing chambers,each balancing chamber comprising a rigid vessel containing a diaphragmdividing the rigid vessel into a first compartment and a secondcompartment, the first compartment of each balancing chamber being influidic communication with the first flow path and the secondcompartment being in fluidic communication with the second flow path.

In another set of embodiments, the cassette includes a first flow pathconnecting a first inlet to a first outlet; a second flow pathconnecting a second inlet to a second outlet; a control fluid path; atleast two pumps, each pump comprising a rigid vessel containing adiaphragm dividing the rigid vessel into a first compartment and asecond compartment, the first compartment of each pump being in fluidiccommunication with the control fluid path and the second compartmentbeing in fluidic communication with the second flow path; and abalancing chamber able to balance flow between the first flow path andthe second flow path.

The cassette, in still another set of embodiments, includes a first flowpath connecting a first inlet to a first outlet, a second flow pathconnecting a second inlet to a second outlet, and a rigid vesselcontaining a diaphragm dividing the rigid vessel into a firstcompartment and a second compartment. In some cases, the firstcompartment are in fluidic communication with the first fluid path andthe second compartment being in fluidic communication with the secondflow path.

Still another aspect of the invention is generally directed at a pump.The pump includes, in one set of embodiments, a first rigid component; asecond rigid component, the second rigid component having on a sidefacing the first plate a groove defined therein, the groove being openin a direction facing the first rigid component; and a diaphragm havinga rim, the rim being held in the groove by a friction fit in the groovebut without contact by the first rigid component against the rim. Insome cases, the first and second rigid components define, at leastpartially, a pod-pump chamber divided by the diaphragm into separatechambers, and further define, at least partially, flow paths into thepod-pump chamber, wherein the groove surrounds the pod-pump chamber.

In another set of embodiments, the pump includes a substantiallyspherical vessel containing a flexible diaphragm dividing the rigidvessel into a first compartment and a second compartment, the firstcompartment and the second compartment not in fluidic communication witheach other, whereby movement of the diaphragm due to fluid entering thefirst compartment causes pumping of fluid within the second compartmentto occur.

In another set of embodiments, the pump is a reciprocatingpositive-displacement pump. In one embodiment, the pump includes a rigidchamber wall; a flexible diaphragm attached to the rigid chamber wall,so that the flexible diaphragm and rigid chamber wall define a pumpingchamber; an inlet for directing flow through the rigid chamber wall intothe pumping chamber; an outlet for directing flow through the rigidchamber wall out of the pumping chamber; a rigid limit wall for limitingmovement of the diaphragm and limiting the maximum volume of the pumpingchamber, the flexible diaphragm and the rigid limit wall forming anactuation chamber; a pneumatic actuation system that intermittentlyprovides a control pressure to the actuation chamber. In some cases, thepneumatic actuation system includes an actuation-chamber pressuretransducer for measuring the pressure of the actuation chamber, a gasreservoir having a first pressure, a variable valve mechanism forvariably restricting gas flowing between the actuation chamber and thegas reservoir, and a controller that receives pressure information fromthe actuation-chamber pressure transducer and controls the variablevalve so as to create the control pressure in the actuation chamber, thecontrol pressure being less than the first pressure.

Still another aspect of the invention is directed to a method. Themethod, in one set of embodiments, includes acts of providing a firstpump comprising a pumping chamber and an actuation chamber, and a secondpump comprising a pumping chamber and an actuation chamber, urging acommon fluid into the actuation chambers of each of the first and secondpumps, and pressurizing the common fluid to pump fluids through each ofthe first and second pumps.

In another set of embodiments, the method includes acts of providing afirst valve comprising a valving chamber and an actuation chamber, and asecond valve comprising a valving chamber and an actuation chamber,urging a common fluid into the actuation chambers of each of the firstand second valves, and pressurizing the common fluid to at leastpartially inhibit fluid flow through each of the first and secondvalves.

In yet another set of embodiments, the method is a method for measuringthe clearance of a dialyzer, the dialyzer being located in a blood flowpath, through which untreated blood can be drawn from a patient andpassed through the dialyzer, and in a dialysate flow path, through whichdialysate can flow from a dialysate supply through the dialyzer, theblood flow path being separated from the dialysate flow path bymembranes in the dialyzer. In one embodiment, the method includes actsof urging a liquid through the dialysate flow path to the dialyzer, soas to keep the membranes wet and prevent the flow of a gas through themembranes, urging a gas through the blood flow path to the dialyzer soas to fill the blood flow path in the dialyzer with the gas, measuringthe volume of gas in the dialyzer, and calculating the clearance of thedialyzer based on the volume of gas measured in the dialyzer.

The method, in still another set of embodiments, is a method formeasuring the clearance of a dialyzer. In one embodiment, the methodincludes acts of applying a pressure differential across the dialyzer,measuring the flowrate of the dialyzer, and determining the clearance ofthe dialyzer based on the pressure differential and the flowrate.

In yet another set of embodiments, the method is a method for measuringthe clearance of a dialyzer. In one embodiment, the method includes actsof passing water through the dialyzer, measuring the amount of ionscollected by the water after passing through the dialyzer, anddetermining the clearance of the dialyzer based on the amount of ionscollected by the water after passing through the dialyzer. In anotherset of embodiments, the method includes acts of passing water throughthe dialyzer, measuring the conductivity of the water, and determiningthe clearance of the dialyzer based on changes in the conductivity ofthe water.

In one set of embodiments, the method is a method for introducing afluid into blood. The method includes, in one embodiment, acts ofproviding a cassette including an integrally formed spike for receivinga vial of fluid, and a valving mechanism for controlling flow of thefluid from the vial into the cassette, attaching a vial containing thefluid to the spike, pumping blood through the cassette, and introducingthe fluid from the vial into the blood.

In one set of embodiments, the method includes acts of providing ahemodialysis system comprising a blood flow path through which untreatedblood is drawn from a patient and passed through a dialyzer, and adialysate flow path through which dialysate flows from a dialysatesupply through the dialyzer, putting the blood flow path and thedialysate flow path into fluidic communication, and urging dialysatethrough the dialysate flow path to cause blood in the blood flow path topass into the patient.

The method, in another set of embodiments, includes acts of providing ahemodialysis system comprising a blood flow path through which untreatedblood is drawn from a patient and passed through a dialyzer, and adialysate flow path through which dialysate flows from a dialysatesupply through the dialyzer, putting the blood flow path and thedialysate flow path into fluidic communication, and urging a gas intothe dialysate flow path to cause flow of blood in the blood flow path.

The method is a method of performing hemodialysis, in still another setof embodiments. In one embodiment, the method includes acts of providinga blood flow path, through which untreated blood can be drawn from apatient and passed through a dialyzer; providing a dialysate flow path,through which dialysate can flow from a dialysate supply through thedialyzer; providing ingredients for preparing a total volume ofdialysate; providing water for mixing with the dialysate ingredients;mixing a volume of water with a portion of the ingredients so as toprepare a first partial volume of dialysate, the first partial volumebeing less than the total volume; pumping the partial volume ofdialysate through the dialysate flow path and through the dialyzer;pumping blood through the blood flow path and through the dialyzer,while the first partial volume of dialysate is being pumped to thedialyzer; and mixing a volume of water with a portion of the ingredientsso as to prepare a second partial volume of dialysate and storing thesecond partial volume of dialysate within a vessel while the blood andthe first partial volume of dialysate are pumped through the dialyzer.

In another embodiment, the method includes acts of passing blood from apatient and dialysate through a dialyzer contained within a hemodialysissystem at a first rate, and forming dialysate within the hemodialysissystem at a second rate that is substantially different from the firstrate, wherein excess dialysate is stored within a vessel containedwithin the hemodialysis system.

In another aspect, the present invention is directed to a method ofmaking one or more of the embodiments described herein, for example, ahemodialysis system. In another aspect, the present invention isdirected to a method of using one or more of the embodiments describedherein, for example, a hemodialysis system.

Other advantages and novel features of the present invention will becomeapparent from the following detailed description of various non-limitingembodiments of the invention when considered in conjunction with theaccompanying figures. In cases where the present specification and adocument incorporated by reference include conflicting and/orinconsistent disclosure, the present specification shall control. If twoor more documents incorporated by reference include conflicting and/orinconsistent disclosure with respect to each other, then the documenthaving the later effective date shall control.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described byway of example with reference to the accompanying figures, which areschematic and are not intended to be drawn to scale. In the figures,each identical or nearly identical component illustrated is typicallyrepresented by a single numeral. For purposes of clarity, not everycomponent is labeled in every figure, nor is every component of eachembodiment of the invention shown where illustration is not necessary toallow those of ordinary skill in the art to understand the invention. Inthe figures:

FIG. 1 is a schematic representation of a hemodialysis system;

FIGS. 2A-2B are high-level schematics of various embodiments of adialysis system;

FIGS. 3A-3B are schematics showing an example of a fluid schematic for adialysis system;

FIG. 4 is a schematic representation of one embodiment of a blood flowcircuit that may be used in a hemodialysis system;

FIG. 5 is a schematic representation of one embodiment of a balancingcircuit that may be used in a hemodialysis system;

FIG. 6 is a schematic representation of a directing circuit that may beused in a hemodialysis system;

FIGS. 7A-7B are schematic representations of mixing circuits that may beused in a hemodialysis system;

FIGS. 8A-8C are graphical representations of phase relationships;

FIG. 9 is a sectional view of a valve that may be incorporated intoembodiments of the fluid-control cassettes;

FIG. 10 is a sectional view of a pod-pump that may be incorporated intoembodiments of the fluid-control cassettes;

FIGS. 11A-11B are schematic views of various pneumatic control systemfor a pod pump;

FIG. 12 is a graph showing how pressures applied to a pod pump may becontrolled;

FIGS. 13A-13B are graphical representations of occlusion detection;

FIG. 14 is a diagram of one embodiment of a control algorithm;

FIG. 15 is a diagram of one embodiment of the controller's standarddiscrete PI regulator;

FIG. 16 is a schematic representation of a dual-housing cassettearrangement according to one embodiment;

FIGS. 17A-17C are schematics relating to the priming of a portion of asystem, in one embodiment of the invention;

FIGS. 18A-18B illustrate the fluid flow of dialysate from a dialysatetank, through the dialyzer and out to drain in one embodiment of theinvention;

FIG. 19 illustrates emptying of a dialysate tank, in another embodimentof the invention;

FIG. 20 illustrates the purging of the system with air at the end oftreatment according to one embodiment of the invention;

FIGS. 21A-21C illustrate the drawing of air in an anticoagulant pump, instill another embodiment of the invention;

FIGS. 22A-22D illustrate integrity tests according to certainembodiments of the invention;

FIG. 23 illustrates a recirculating flow path, in another embodiment ofthe invention;

FIGS. 24A-24D illustrate the priming of a system with dialysate, in yetanother embodiment of the invention;

FIG. 25 illustrates the priming of an anticoagulant pump, in stillanother embodiment of the invention;

FIGS. 26A-26F illustrate the removal of dialysate from a blood flowcircuit, in one embodiment of the invention;

FIGS. 27A-27C illustrate the delivery of a bolus of anticoagulant to apatient, in another embodiment of the invention;

FIG. 28 illustrates solution infusion, in one embodiment of theinvention;

FIGS. 29A-29B are schematic representations showing how an emergencyrinse-back procedure can be implemented;

FIGS. 30A and 30B are isometric and top views of an outer top plate ofan exemplary embodiment of the cassette;

FIGS. 30C and 30D are isometric and top views of an inner top plate ofan exemplary embodiment of the cassette;

FIG. 30E is a side view of the top plate of an exemplary embodiment ofan cassette;

FIGS. 31A and 31B are isometric and top views of the liquid side of amidplate according to an exemplary embodiment of the cassette;

FIGS. 31C and 31D are isometric and top views of the air side of amidplate according to an exemplary embodiment of the cassette;

FIGS. 32A and 32B are isometric and top views of the inner side of abottom plate according to an exemplary embodiment of the cassette;

FIGS. 32C and 32D are isometric and top views of the outer side of abottom plate according to an exemplary embodiment of the cassette;

FIG. 32E is a side view of a bottom plate according to an exemplaryembodiment of the cassette;

FIG. 33A is a top view of an assembled exemplary embodiment of acassette with a vial attached;

FIG. 33B is a bottom view of an assembled exemplary embodiment of acassette with a vial attached;

FIG. 33C is an exploded view of an assembled exemplary embodiment of acassette with a vial;

FIG. 33D is an exploded view of an assembled exemplary embodiment of acassette with a vial;

FIG. 34A is an isometric bottom view of an exemplary embodiment of themidplate of an exemplary embodiment of the cassette;

FIG. 34B is an isometric top view of the midplate of an exemplaryembodiment of a cassette;

FIG. 34C is an isometric bottom view of an exemplary embodiment of themidplate of a cassette;

FIG. 34D is a side view of an exemplary embodiment of the midplate of acassette;

FIGS. 35A-35B are isometric and top views of an exemplary embodiment ofthe top plate of an exemplary embodiment of the cassette;

FIGS. 35C-35D are isometric views of an exemplary embodiment of the topplate of an exemplary embodiment of the cassette;

FIG. 35E is a side view of an exemplary embodiment of the top plate of acassette;

FIGS. 36A and 36B are isometric bottom views of an exemplary embodimentof the bottom plate of an exemplary embodiment of a cassette;

FIGS. 36C and 36D are isometric top views of an exemplary embodiment ofthe bottom plate of an exemplary embodiment of a cassette;

FIG. 36E is a side view of an exemplary embodiment of the bottom plateof an exemplary embodiment of a cassette;

FIG. 37 is an isometric front view of an exemplary embodiment of theactuation side of the midplate of a cassette with the valves indicatedcorresponding to FIG. 36;

FIG. 38A is a view of an exemplary embodiment of the outer top plate ofa cassette;

FIG. 38B is a view of an exemplary embodiment of the inner top plate ofa cassette;

FIG. 38C is a side view of an exemplary embodiment of the top plate of acassette;

FIG. 39A is a view of an exemplary embodiment of the fluid side of themidplate of a cassette;

FIG. 39B is a front view of an exemplary embodiment of the air side ofthe midplate of a cassette;

FIG. 39C is a side view of an exemplary embodiment of the midplate of acassette;

FIG. 40A is a view of an exemplary embodiment of the inner side of thebottom plate of a cassette;

FIG. 40B is a view of an exemplary embodiment of the outer side of thebottom plate of a cassette;

FIG. 40C is a side view of an exemplary embodiment of the midplate of acassette;

FIGS. 41A and 41B are isometric and front views of an exemplaryembodiment of the outer top plate of an exemplary embodiment of acassette;

FIGS. 41C and 41D are isometric and front views of an exemplaryembodiment of the inner top plate of a cassette;

FIG. 41E is a side view of the top plate of an exemplary embodiment of acassette;

FIGS. 42A and 42B are isometric and front views of an exemplaryembodiment of the liquid side of the midplate of a cassette;

FIGS. 42C and 42D are isometric and front views of an exemplaryembodiment of the air side of the midplate of a cassette;

FIG. 42E is a side view of the midplate according to an exemplaryembodiment of a cassette;

FIGS. 43A and 43B are isometric and front views of the inner side of abottom plate according to an exemplary embodiment of a cassette;

FIGS. 43C and 43D are isometric and front views of an exemplaryembodiment of the outer side of the bottom plate of a cassette;

FIG. 43E is a side view of a bottom plate according to an exemplaryembodiment of a cassette;

FIG. 44A is a top view of an assembled exemplary embodiment of acassette;

FIG. 44B is a bottom view of an assembled exemplary embodiment of acassette;

FIG. 44C is an exploded view of an assembled exemplary embodiment of acassette;

FIG. 44D is an exploded view of an assembled exemplary embodiment of acassette;

FIG. 45 shows a cross sectional view of an exemplary embodiment of anassembled cassette;

FIG. 46A is a front view of the assembled exemplary embodiment of thecassette system;

FIG. 46B is an isometric view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46C is an isometric view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46D is an exploded view of the assembled exemplary embodiment ofthe cassette system;

FIG. 46E is an exploded view of the assembled exemplary embodiment ofthe cassette system;

FIG. 47A is an isometric view of an exemplary embodiment of the pod ofthe cassette system;

FIG. 47B is an isometric view of an exemplary embodiment of the pod ofthe cassette system;

FIG. 47C is a side view of an exemplary embodiment of the pod of thecassette system;

FIG. 47D is an isometric view of an exemplary embodiment of one half ofthe pod of the cassette system;

FIG. 47E is an isometric view of an exemplary embodiment of one half ofthe pod of the cassette system;

FIG. 48A is a pictorial view of the exemplary embodiment of the podmembrane of the cassette system;

FIG. 48B is a pictorial view of the exemplary embodiment of the podmembrane of the cassette system;

FIG. 49 is an exploded view of an exemplary embodiment of the pod of thecassette system;

FIG. 50A is an exploded view of one embodiment of a check valve fluidline in the cassette system;

FIG. 50B is an exploded view of one embodiment of a check valve fluidline in the cassette system;

FIG. 50C is an isometric view of an exemplary embodiment of a fluid linein the cassette system;

FIG. 51A is one embodiment of the fluid flow-path schematic of thecassette system integrated;

FIG. 51B is one embodiment of the fluid flow-path schematic of thecassette system integrated;

FIGS. 52A-52F are various views of one embodiment of the block forconnecting the pneumatic tubes to the manifold according to oneembodiment of the present system;

FIG. 53 is a view of another exemplary sensor manifold;

FIG. 54 is a view of the fluid paths within the exemplary sensormanifold shown in FIG. 53;

FIG. 55 is a side view of the exemplary sensor manifold shown in FIG.53;

FIG. 56A is a cross sectional view of the exemplary sensor manifoldshown in FIG. 53 at cross section A-A of FIG. 56B;

FIG. 56B is a front view of the exemplary sensor manifold shown in FIG.53;

FIG. 57 is an exploded view of the exemplary sensor manifold shown inFIG. 53;

FIG. 58 is a view of a printed circuit board and media edge connector inaccordance with the exemplary sensor manifold shown in FIG. 53; and

FIG. 59 is an exemplary fluid schematic of a hemodialysis system.

DETAILED DESCRIPTION

The present invention generally relates to hemodialysis and similardialysis systems, including a variety of systems and methods that wouldmake hemodialysis more efficient, easier, and/or more affordable. Oneaspect of the invention is generally directed to new fluid circuits forfluid flow. In one set of embodiments, a hemodialysis system may includea blood flow path and a dialysate flow path, where the dialysate flowpath includes one or more of a balancing circuit, a mixing circuit,and/or a directing circuit. Preparation of dialysate by the mixingcircuit, in some instances, may be decoupled from patient dialysis. Insome cases, the circuits are defined, at least partially, within one ormore cassettes, optionally interconnected with conduits, pumps, or thelike. In one embodiment, the fluid circuits and/or the various fluidflow paths may be at least partially isolated, spatially and/orthermally, from electrical components of the hemodialysis system. Insome cases, a gas supply may be provided in fluid communication with thedialysate flow path and/or the dialyzer that, when activated, is able tourge dialysate to pass through the dialyzer and urge blood in the bloodflow path back to the patient. Such a system may be useful, for example,in certain emergency situations (e.g., a power failure) where it isdesirable to return as much blood to the patient as possible. Thehemodialysis system may also include, in another aspect of theinvention, one or more fluid handling devices, such as pumps, valves,mixers, or the like, which can be actuated using a control fluid, suchas air. In some cases, the control fluid may be delivered to the fluidhandling devices using an external pump or other device, which may bedetachable in certain instances. In one embodiment, one or more of thefluid handling devices may be generally rigid (e.g., having a spheroidshape), optionally with a diaphragm contained within the device,dividing it into first and second compartments.

Various aspects of the present invention are generally directed to newsystems for hemodialysis and the like, such as hemofiltration systems,hemodiafiltration systems, plasmaphoresis systems, etc. Accordingly,although the various systems and methods described herein are describedin relation to hemodialysis, it should be understood that the varioussystems and method described herein are applicable to other dialysissystems and/or in any extracorporeal system able to treat blood or otherbodily fluids, such as plasma.

As discussed above, a hemodialysis system typically includes a bloodflow path and a dialysate flow path. It should be noted that within suchflow paths, the flow of fluid is not necessarily linear, and there maybe any number of “branches” within the flow path that a fluid can flowfrom an inlet of the flow path to an outlet of the flow path. Examplesof such branching are discussed in detail below. In the blood flow path,blood is drawn from a patient, and is passed through a dialyzer, beforebeing returned to the patient. The blood is treated by the dialyzer, andwaste molecules (e.g., urea, creatinine, etc.) and water are passed fromthe blood, through the dialyzer, into a dialysate solution that passesthrough the dialyzer by the dialysate flow path. In various embodiments,blood may be drawn from the patient from two lines (e.g., an arterialline and a venous line, i.e., “dual needle” flow), or in some cases,blood may be drawn from the patient and returned through the same needle(e.g., the two lines may both be present within the same needle, i.e.,“single needle” flow). In still other embodiments, a “Y” site or “T”site is used, where blood is drawn from the patient and returned to thepatient through one patient connection having two branches (one beingthe fluid path for the drawn blood, the second the fluid path for thereturn blood). The patient may be any subject in need of hemodialysis orsimilar treatments, although typically the patient is a human. However,hemodialysis may be performed on non-human subjects, such as dogs, cats,monkeys, and the like.

In the dialysate flow path, fresh dialysate is prepared and is passedthrough the dialyzer to treat the blood from the blood flow path. Thedialysate may also be equalized for blood treatment within the dialyzer(i.e., the pressure between the dialysate and the blood are equalized),i.e., the pressure of dialysate through the dialyzer is closely matchedto the pressure of blood through the dialyzer, often exactly, or in someembodiments, at least within about 1% or about 2% of the pressure of theblood. After passing through the dialyzer, the used dialysate,containing waste molecules (as discussed below), is discarded in somefashion. In some cases, the dialysate is heated prior to treatment ofthe blood within the dialyzer using an appropriate heater, such as anelectrical resistive heater. The dialysate may also be filtered toremove contaminants, infectious organisms, debris, and the like, forinstance, using an ultrafilter. The ultrafilter may have a mesh sizechosen to prevent species such as these from passing therethrough. Forinstance, the mesh size may be less than about 0.3 micrometers, lessthan about 0.2 micrometers, less than about 0.1 micrometers, or lessthan about 0.05 micrometers, etc. The dialysate is used to draw wastemolecules (e.g., urea, creatinine, ions such as potassium, phosphate,etc.) and water from the blood into the dialysate through osmosis, anddialysate solutions are well-known to those of ordinary skill in theart.

The dialysate typically contains various ions such as potassium andcalcium that are similar to their natural concentration in healthyblood. In some cases, the dialysate may contain sodium bicarbonate,which is usually at a concentration somewhat higher than found in normalblood. Typically, the dialysate is prepared by mixing water from a watersupply with one or more ingredients: an “acid” (which may containvarious species such as acetic acid, dextrose, NaCl, CaCl, KCl, MgCl,etc.), sodium bicarbonate (NaHCO₃), and/or sodium chloride (NaCl). Thepreparation of dialysate, including using the appropriate concentrationsof salts, osmolarity, pH, and the like, is well-known to those ofordinary skill in the art. As discussed in detail below, the dialysateneed not be prepared at the same rate that the dialysate is used totreat the blood. For instance, the dialysate can be made concurrently orprior to dialysis, and stored within a dialysate storage vessel or thelike.

Within the dialyzer, the dialysate and the blood typically do not comeinto physical contact with each other, and are separated by asemipermeable membrane. Typically, the semipermeable membrane is formedfrom a polymer such as cellulose, polyarylethersulfone, polyamide,polyvinylpyrrolidone, polycarbonate, polyacrylonitrile, or the like,which allows the transport of ions or small molecules (e.g., urea,water, etc.), but does not allow bulk transport or convection duringtreatment of the blood. In some cases, even larger molecules, such asbeta-2-microglobulin, may pass through the membrane.

The dialysate and the blood do not come into contact with each other inthe dialyzer, and are usually separated by the membrane. Often, thedialyzer is constructed according to a “shell-and-tube” designcomprising a plurality of individual tubes or fibers (through whichblood flows), formed from the semipermeable membrane, surrounded by alarger “shell” through which the dialysate flows (or vice versa in somecases). Flow of the dialysate and the blood through the dialyzer can becountercurrent, or cocurrent in some instances. Dialyzers are well-knownto those of ordinary skill in the art, and are obtainable from a numberof different commercial sources.

In one aspect, the dialysate flow path can be divided into one or morecircuits, such as a balancing circuit, a mixing circuit, and/or adirecting circuit. It should be noted that a circuit, in reference tofluid flow, is not necessarily fluidically isolated, i.e., fluid mayflow into a fluid circuit and out of a fluid circuit. Similarly, a fluidmay pass from one fluid circuit to another fluid circuit when the fluidcircuits are in fluid communication or are fluidly connected to eachother. It should be noted that, as used herein, “Fluid” means anythinghaving fluidic properties, including but not limited to, gases such asair, and liquids such as water, aqueous solution, blood, dialysate, etc.

A fluid circuit is typically a well-defined module that receives acertain number of fluid inputs and in some cases performs one or moretasks on the fluid inputs, before directing the fluids to appropriateoutputs. In certain embodiments of the invention, as discussed below,the fluid circuit is defined as a cassette. As a specific example, adialysate flow path may include a balancing circuit, a directingcircuit, and a mixing circuit. As another example, a blood flow path mayinclude a blood flow circuit. Within the balancing circuit, dialysate isintroduced into the balancing circuit and pumps operate on the dialysatesuch that the pressure of dialysate passing through the dialyzerbalances the pressure of blood passing through the dialysate, aspreviously discussed. Similarly, within the directing circuit, freshdialysate is passed from the mixing circuit to the balancing circuit,while used dialysate is passed from the balancing circuit to a drain.Within the mixing circuit, ingredients and water are mixed together toform fresh dialysate. The blood flow circuit is used to draw blood fromthe patient, pass the blood through a dialyzer, and return the blood tothe patient. These circuits will be discussed in detail below.

An example of a hemodialysis system having such fluid circuits isillustrated schematically in FIG. 2A as a high-level overview. FIG. 2Aillustrates a dialysis system 5 that includes a blood flow circuit 10,through which blood passes from a patient to a dialyzer 14, and throughwhich treated blood returns to the patient. The hemodialysis system inthis example also includes a balancing circuit or an internal dialysatecircuit 143, which takes dialysate after it passes through anultrafilter 73 and passes the dialysate through dialyzer 14, with useddialysate returning to balancing circuit 143 from dialyzer 14. Adirecting circuit or an external dialysate circuit 142 handles freshdialysate before it passes through ultrafilter 73. A mixing circuit 25prepares dialysate, for instance, on an as-needed basis, during and/orin advance of dialysis, etc., using various ingredients 49 and water.The directing circuit 142 can also receive water from a water supply 30and pass it to mixing circuit 25 for preparation of the dialysate, andthe directing circuit 142 can also receive used dialysate from balancingcircuit 143 and pass it out of system 5 as waste via drain 31. Alsoshown, in dotted lines, are conduits 67 that can be connected betweenblood flow circuit 10, and directing circuit 142, e.g., for disinfectionof the hemodialysis system. In one set of embodiments, one or more ofthese circuits (e.g., the blood flow circuit, the balancing circuit, thedirecting circuit, and/or the mixing circuit) may include a cassetteincorporating the valves and pumps needed for controlling flow throughthat portion. Examples of such systems are discussed in detail below.

FIG. 2B is a schematic representation of a hemodialysis system accordingto one embodiment of the invention. In this schematic, a blood flowcassette 22 is used to control flow through the blood flow circuit 10,and a dialysate cassette 21 is used to control flow through thedialysate circuit. The blood flow cassette includes at least one inletvalve 24 (in other embodiments, more than one inlet valve is included)to control the flow of blood through cassette 22 as well as ananticoagulant valve or pump 12 to control the flow of anticoagulant intothe blood, and a blood flow pump 13, which may include a pair of podpumps in some cases. These pod pumps may be of the type (or variationsof the type) as described in U.S. Provisional Patent Application Ser.No. 60/792,073, filed Apr. 14, 2006, entitled “Extracorporeal ThermalTherapy Systems and Methods”; or in U.S. Pat. No. 8,292,594, issued Oct.23, 2012 and entitled “Fluid Pumping Systems, Devices and Methods,” eachof which is incorporated herein in its entirety. All the pumps andvalves in this example system may be controlled by a control system,e.g., an electronic and digital control system, although other controlsystems are possible in other embodiments.

Providing two pod pumps may allow for a more continuous flow of bloodthrough the blood flow circuit 10; however, a single pod pump, such as asingle pod pump may be used in other embodiments. The pod pumps mayinclude active inlet and outlet valves (instead of passive check valvesat their inlets and outlets) so that flow in the blood flow circuit 10may be reversed under some conditions. For instance, by reversing flowin the blood flow circuit, the hemodialysis system can check whether theoutlet of the blood flow circuit is properly connected to the patient sothat the treated blood is correctly returned to the patient. If, forexample, the patient connection point has been disconnected, e.g., byfalling out, reversing the blood flow pump would draw air rather thanblood. This air can be detected by standard air detectors incorporatedinto the system.

In another embodiment, blood outlet valve 26 and air trap/filter 19,which are located downstream of the dialyzer, may be incorporated intoblood flow cassette 22. The pod pumps and all the valves (including thevalves associated with the pod pumps' inlets and outlets) in the bloodflow cassette 22 may be actuated pneumatically. Sources of positive andnegative gas pressure in one embodiment, are provided by a base unitholding cassette or other device holding the cassette. However, in otherembodiments, the positive and negative gas pressure may be provided byan external device fluidly connected to the cassettes, or any devicebuild into the system The pump chamber may be actuated in the mannerdescribed in U.S. Provisional Patent Application Ser. No. 60/792,073,filed Apr. 14, 2006, entitled “Extracorporeal Thermal Therapy Systemsand Methods”; or in U.S. Pat. No. 8,292,594, issued Oct. 23, 2012 andentitled “Fluid Pumping Systems, Devices and Methods,” referred tohereinabove. For instance, the pumps may be controlled and the end ofstroke detected in the manner described below. The blood flow cassette22 may also contain an integrally formed spike for receiving a vial ofanticoagulant.

The anticoagulant pump, in one embodiment, includes three fluid valves(which may be controlled with a control fluid) and a single pumpingcompartment (although there may be more than one pumping compartment inother embodiments. The valves may connect the compartment to a filteredair vent, to a vial of anticoagulant (or other anticoagulant supply,such as a bag or a bottle, etc.), or to the blood flow path. Theanticoagulant pump can be operated by sequencing the opening and closingof the fluid valves and controlling the pressure in the pumpcompartment, e.g., via the control fluid. When the anticoagulant isremoved from the vial it may be replaced with an equal volume of air,e.g., to keep pressure within the vial relatively constant. Thisreplacement of anticoagulant volume with air may be accomplished, forexample, by (i) opening the valve from the filtered air vent to the pumpcompartment, (ii) drawing air into the compartment by connecting thenegative pressure source to the chamber, (iii) closing the air ventvalve, (iv) opening the valve connecting the compartment to the vial,and (v) pushing air into the vial by connecting the positive pressuresource to the compartment. The anticoagulant can be pumped from the vialinto the blood flow path with a similar sequence, using the valves tothe vial and the blood path rather than the valves to the air vent andthe vial.

FIG. 3A is a schematic diagram showing a specific embodiment of thegeneral overview shown in FIG. 2A. FIG. 3A shows, in detail, how a bloodflow circuit 141, a balancing circuit 143, a directing circuit 142, anda mixing circuit 25 can be implemented on cassettes and made tointerrelate with each other and to a dialyzer 14, an ultrafilter 73,and/or a heater 72, in accordance with one embodiment of the invention.It should be understood, of course, that FIG. 3A is only one possibleembodiment of the general hemodialysis system of FIG. 2A, and in otherembodiments, other fluid circuits, modules, flow paths, layouts, etc.are possible. Examples of such systems are discussed in more detailbelow, and also can be found in the following, each of which isincorporated herein by reference: U.S. Provisional Patent ApplicationSer. No. 60/903,582, filed Feb. 27, 2007, entitled “Hemodialysis Systemand Methods”; U.S. Provisional Patent Application Ser. No. 60/904,024,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods”; U.S.patent application Ser. No. 11/871,680, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,712, filedOct. 12, 2007, entitled “Pumping Cassette”; U.S. patent application Ser.No. 11/871,787, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,793, filed Oct. 12, 2007, entitled“Pumping Cassette”; or U.S. patent application Ser. No. 11/871,803,filed Oct. 12, 2007, entitled “Cassette System Integrated Apparatus.”

The components in FIG. 3A will be discussed in detail below. Briefly,blood flow circuit 141 includes an anticoagulant supply 11 and a bloodflow pump 13 which pumps blood from a patient to a dialyzer 14. Theanticoagulant supply 11, although shown in the path of blood flowingtowards the dialyzer, in other embodiments, may be instead located inthe path of blood flowing towards the patient, or in another suitablelocation. The anticoagulant supply 11 may be placed in any locationdownstream from blood flow pump 13. Balancing circuit 143 includes twodialysate pumps 15, which also pump dialysate into dialyzer 14, and abypass pump 35. Directing circuit 142 includes a dialysate pump 159,which pumps dialysate from dialysate tank 169 through heater 72 and/orultrafilter 73 to the balancing circuit. Directing circuit 142 alsotakes waste fluid from balancing circuit 143 and directs it to a drain31. In some cases, the blood flow circuit 141 can be connected viaconduits 67 to directing circuit 142, e.g., for disinfection, asdiscussed below. Dialysate flows into dialysate tank 169 from adialysate supply. In one embodiment, as is shown in FIG. 3A, thedialysate is produced in mixing circuit 25. Water from water supply 30flows through directing circuit 142 into mixing circuit 25. Dialysateingredients 49 (e.g., bicarbonate and acid) are also added into mixingcircuit 25, and a series of mixing pumps 180, 183, 184 are used toproduce the dialysate, which is then sent to directing circuit 142.

In this example system, one of the fluid circuits is a blood flowcircuit, e.g., blood flow circuit 141 in FIG. 3A. In the blood flowcircuit, blood from a patient is pumped through a dialyzer and then isreturned to the patient. In some cases, blood flow circuit isimplemented on a cassette, as discussed below, although it need not be.The flow of blood through the blood flow circuit, in some cases, isbalanced with the flow of dialysate flowing through the dialysate flowpath, especially through the dialyzer and the balancing circuit.

One example of a blood flow circuit is shown in FIG. 4. Generally, bloodflows from a patient through arterial line 203 via blood flow pump 13 todialyzer 14 (the direction of flow during normal dialysis is indicatedby arrows 205; in some modes of operation, however, the flow may be indifferent directions, as discussed below). Optionally, an anticoagulantmay be introduced into the blood via anticoagulant pump 80 from ananticoagulant supply. As shown in FIG. 4, the anticoagulant can enterthe blood flow path after the blood has passed through blood flow pump13; however, the anticoagulant may be added in any suitable locationalong the blood flow path in other embodiments. In other embodiments,anticoagulant supply 11 may be located anywhere downstream from theblood flow pump. After passing through dialyzer 14 and undergoingdialysis, the blood returns to the patient through venous line 204,optionally passing through air trap and/or a blood sample port 19.

As is shown in FIG. 4, blood flow cassette 141 also includes one or moreblood flow pumps 13 for moving blood through the blood flow cassette.The pumps may be, for instance, pumps that are actuated by a controlfluid, such as is discussed below. For instance, in one embodiment, pump13 may comprise two (or more) pod pumps, e.g., pod pumps 23 in FIG. 4.Each pod pump, in this particular example, may include a rigid chamberwith a flexible diaphragm or membrane dividing each chamber into a fluidcompartment and control compartment. There are four entry/exit valves onthese compartments, two on the fluid compartment and two on the controlcompartment. The valves on the control compartment of the chambers maybe two-way proportional valves, one connected to a first control fluidsource (e.g., a high pressure air source), and the other connected to asecond control fluid source (e.g., a low pressure air source) or avacuum sink. The fluid valves on the compartments can be opened andclosed to direct fluid flow when the pod pumps are pumping. Non-limitingexamples of pod pumps are described in U.S. Provisional PatentApplication Ser. No. 60/792,073, filed Apr. 14, 2006, entitled“Extracorporeal Thermal Therapy Systems and Methods”; or in U.S. Pat.No. 8,292,594, issued Oct. 23, 2012 and entitled “Fluid Pumping Systems,Devices and Methods,” each incorporated herein by reference. Furtherdetails of the pod pumps are discussed below. If more than one pod pumpis present, the pod pumps may be operated in any suitable fashion, e.g.,synchronously, asynchronously, in-phase, out-of-phase, etc.

For instance, in some embodiments, the two pump pumps can be cycled outof phase to affect the pumping cycle, e.g., one pump chamber fills whilethe second pump chamber empties. A phase relationship anywhere between0° (the pod pumps act in the same direction) and 180° (the pod pumps actin opposite directions) can be selected in order to impart any desiredpumping cycle.

A phase relationship of 180° may yield continuous flow into and out ofthe pod pump. This is useful, for instance, when continuous flow isdesired, e.g., for use with dual needle flow or a “Y” or “T” connection.Setting a phase relationship of 0°, however, may be useful in some casesfor single needle flow or in other cases. In a 0° relationship, the podpumps will first fill from the needle, then deliver blood through theblood flow path and back to the patient using the same needle. Inaddition, running at phases between 0° and 180° can be used in somecases, to achieve a push/pull relationship (hemodiafiltration orcontinuous back flush) across the dialyzer. FIGS. 8A-8C are graphicalrepresentations of examples of such phase relationships. In thesefigures, the volume or flow of each pod pump, the volumes of each podpumps, and the total hold up volume of both pod pumps is shown as afunction of time. These times and flowrates are arbitrarily chosen, andare presented here to illustrate the relationships between the pod pumpsat different phasings. For instance, at a 180° phase relationship (FIG.8B), the total hold up volume remains substantially constant.

In some cases, an anticoagulant (e.g., heparin, or any otheranticoagulant known to those of ordinary skill in the art) may be mixedwith the blood within blood flow cassette 141 as is shown in FIG. 14.For instance, the anticoagulant may be contained within a vial 11 (orother anticoagulant supply, such as a tube or a bag), and blood flowcassette 141 may be able to receive the anticoagulant vial with anintegrally formed spike 201 (which, in one embodiment, is a needle) thatcan pierce the seal of the vial. The spike may be formed from plastic,stainless steel, or another suitable material, and may be a sterilizablematerial in some cases, e.g., the material may be able to withstandsufficiently high temperatures and/or radiation so as to sterilize thematerial. As an example, as is shown in FIG. 4, spike 201 may beintegrally formed with a blood flow cassette 141, and a vial 11 can beplaced onto the spike, piercing the seal of the vial, such thatanticoagulant can flow into blood flow cassette to be mixed with theblood in the blood flow path, or in some cases, mixed with dialysate asdiscussed below.

A third pump 80, which can act as a metering chamber in some cases, inblood flow cassette 141 can be used to control the flow of anticoagulantinto the blood within the cassette. Third pump 80 may be of the same orof a different design than pump 13. For instance, third pump 80 may be apod pump and/or third pump 80 may be actuated by a control fluid, suchas air. For instance, as is shown in FIG. 4, third pump 80 may include arigid chamber with a flexible diaphragm dividing the chamber into afluid compartment and a control compartment. Valves on the controlcompartment of the chamber may be connected to a first control fluidsource (e.g., a high pressure air source), and the other compartmentconnected to a second control fluid source (e.g., a low pressure airsource) or a vacuum sink. Valves on the fluid compartment of the chambercan be opened and closed in response to the control compartment, thuscontrolling the flow of anticoagulant into the blood. Further details ofsuch a pod pump are discussed below. In one set of embodiments, air mayalso be introduced into the blood flow path through a filter 81, asdiscussed below.

In some cases, the anticoagulant pump is an FMS pump. The FMS algorithmuses changes in pressures to calculate a volume measurement at the endof a fill stroke and at the end of a delivery stroke. The differencebetween the computed volumes at the end of a fill and delivery stroke isthe actual stroke volume. This actual stroke volume can be compared toan expected stroke volume for the particular sized chamber. If theactual and expected volumes are significantly different, the stroke hasnot properly completed and an error message can be generated.

If stroke volumes are collected with a scale, the calculation can beworked backwards to determine a calibration value for the referencechamber. FMS systems can vent to atmosphere for the FMS measurement.Alternatively, the system can vent to a high pressure positive sourceand a low pressure negative source for the FMS measurement. Doing soprovides the following advantages, amongst others: (1) if the highpressure source is a pressure reservoir with a controlled pressure,there is an opportunity to do a cross check on the pressure sensors ofthe reservoir and chamber to ensure they are similar when the chamber isbeing vented to the reservoir. This can be used to detect a brokenpressure sensor or a failed valve; (2) by using higher/lower pressuresto vent, there are larger pressure differences for the FMS measurementsso better resolution can be obtained.

Blood flow circuit 141 may also include an air trap 19 incorporated intoblood flow circuit 141 in some cases. Air trap 19 may be used to removeair bubbles that may be present within the blood flow path. In somecases, air trap 19 is able to separate any air that may be present fromthe blood due to gravity. In some cases, air trap 19 may also include aport for sampling blood. Air traps are known to those of ordinary skillin the art.

Additional fluid connections 82 may allow blood flow circuit 10 to alsobe connected to the patient, and/or to a fluid source for priming ordisinfecting the system, including blood flow circuit 10. Generally,during disinfection, arterial line 203 and venous line 204 are connecteddirectly to directing circuit 142 via conduits 67, such that adisinfecting fluid (e.g., heated water and in some embodiments, acombination heated water and one or more chemical agent) may be flowedthrough dialyzer 14 and blood flow circuit 141 back to directing circuit142 for recirculation, this disinfection is similar to those shown inU.S. Pat. No. 5,651,898 to Kenley, et al., which is incorporated hereinby reference. This is also discussed in more detail below.

The pressure within arterial line 203, to draw blood from the patient,may be kept to a pressure below atmospheric pressure in some cases. If apod pump is used, the pressure within blood flow pump 13 may beinherently limited to the pressures available from the positive andnegative pressure reservoirs used to operate the pump. In the event thata pressure reservoir or valve fails, the pump chamber pressure willapproach the reservoir pressure. This will increase the fluid pressureto match the reservoir pressure until the diaphragm within the pod pump“bottoms” (i.e., is no longer is able to move, due to contact with asurface), and the fluid pressure will not exceed a safe limit and willequilibrate with a natural body fluid pressure. This failure naturallystops operation of the pod pump without any special intervention.

A specific non-limiting example of a blood flow cassette is shown inFIGS. 30-33. Referring now to FIGS. 30A and 30B, the outer side of thetop plate 900 of an exemplary embodiment of the cassette is shown. Thetop plate 900 includes one half of the pod pumps 820, 828. This half isthe liquid half where the source fluid will flow through. The two fluidpaths 818, 812 are shown. These fluid paths lead to their respective podpumps 820, 828.

The pod pumps 820, 828 include a raised flow path 908, 910. The raisedflow path 908, 910 allows for the fluid to continue to flow through thepod pumps 820, 828 after the diaphragm (not shown) reaches the end ofstroke. Thus, the raised flow path 908, 910 minimizes the diaphragmcausing air or fluid to be trapped in the pod pump 820, 828 or thediaphragm blocking the inlet or outlet of the pod pump 820, 828, whichwould inhibit continuous flow. The raised flow path 908, 910 is shown inone exemplary embodiment having particular dimensions, and in somecases, the dimensions are equivalent to the fluid flow paths 818, 812.However, in alternate embodiments, the raised flow path 908, 910 isnarrower, or in still other embodiments, the raised flow path 908, 910can be any dimensions as the purpose is to control fluid flow so as toachieve a desired flow rate or behavior of the fluid. In someembodiments, the raised flow path 908, 910 and the fluid flow paths 818,812 have different dimensions. Thus, the dimensions shown and describedhere with respect to the raised flow path, the pod pumps, the valves orany other aspect are mere exemplary and alternate embodiments. Otherembodiments are readily apparent.

In one exemplary embodiment of this cassette, the top plate includes aspike 902 as well as a container perch 904. The spike 902 is hollow inthis example, and is fluidly connected to the flow path. In someembodiments, a needle is attached into the spike. In other embodiments,a needle is connected to the container attachment.

Referring now to FIGS. 30C and 30D, the inside of the top plate 900 isshown. The raised flow paths 908, 910 connects to the inlet flow paths912, 916 and outlet flow paths 914, 918 of the pod pumps 820, 828. Theraised flow paths are described in more detail above.

The metering pump (not shown) includes connection to an air vent 906 aswell as connection to the spike's hollow path 902. In one exemplaryembodiment, the air vent 906 includes an air filter (not shown). The airfilter may be a particle air filter in some cases. In some embodiments,the filter is a somicron hydrophobic air filter. In various embodiments,the size of the filter may vary, in some instances the size will dependon desired outcome. The metering pump works by taking air in through theair vent 906, pumping the air to the container of second fluid (notshown) through the spike's hollow path 902 and then pumping a volume ofsecond fluid out of the container (not shown) through the spike's hollowpath 902 and into the fluid line at point 826. This fluid flow path forthe metering pump is shown with arrows on FIG. 30C.

Referring now to FIGS. 31A and 31B, the liquid side of the midplate 1000is shown. The areas complementary to the fluid paths on the inner topplate are shown. These areas are slightly raised tracks that present asurface finish that is conducive to laser welding, which is the mode ofmanufacture in one embodiment. The fluid inlet 810 and fluid outlet 824are also shown in this view.

Referring next to FIGS. 31C and 31D, the air side of the midplate 1000is shown according to one embodiment. The air side of the valve holes808, 814, 816, 822 correspond to the holes in the fluid side of themidplate (shown in FIG. 31A). As seen in FIGS. 33C and 33D, diaphragms1220 complete valves 808, 814, 816, 822 while diaphragms 1226 completepod pumps 820, 828. The metering pump 830 is completed by diaphragm1224. The valves 808, 814, 816, 822, 832, 834, 836 are actuatedpneumatically, and as the diaphragm is pulled away from the holes,liquid is drawn in, and as the diaphragm is pushed toward the holes,liquid is pushed through. The fluid flow is directed by the opening andclosing of the valves 808, 814, 816, 822, 832, 834, 836.

Referring to FIGS. 31A and 31C, the metering pump includes three holes,1002, 1004, 1006. One hole 1002 pulls air into the metering pump, thesecond hole 1004 pushes air to the spike/source container and also,draws liquid from the source container, and the third hole 1006 pushesthe second fluid from the metering pump 830 to the fluid line to point826.

Valves 832, 834, 836 actuate the second fluid metering pump. Valve 832is the second fluid/spike valve, valve 834 is the air valve and valve836 is the valve that controls the flow of fluid to the fluid line toarea 826.

Referring next to FIGS. 32A and 32B, the inner view of the bottom plate1100 is shown. The inside view of the pod pumps 820, 828, the meteringpump 830 and the valves 808, 814, 816, 822, 832, 834, 836 actuation/airchamber is shown. The pod pumps 820, 828, metering pump 830 and thevalves 808, 814, 816, 822, 832, 834, 836 are actuated by a pneumatic airsource. Referring now to FIGS. 32C and 32D, the outer side of the bottomplate 1100 is shown. The source of air is attached to this side of thecassette. In one embodiment, tubes connect to the features on the valvesand pumps 1102. In some embodiments, the valves are ganged, and morethan one valve is actuated by the same air line.

Referring now to FIGS. 33A and 33B, an assembled cassette 1200 with acontainer (or other source) of a second fluid 1202 is shown, which, inthis embodiment, may be an anticoagulant as described above, attached isshown. The container 1202 contains the source of the second fluid and isattached to the spike (not shown) by a container attachment 1206. Theair filter 1204 is shown attached to the air vent (not shown, shown inFIG. 30A as 906). Although not visible in FIG. 33A, the container perch(shown in FIG. 30A as 904) is under the container attachment 1206. Anexploded view of the assembled cassette 1200 shown in FIGS. 33A and 12Bis shown in FIGS. 33C and 33D. In these views, an exemplary embodimentof the pod pump diaphragms 1226 is shown. The gasket of the diaphragmprovides a seal between the liquid chamber (in the top plate 900) andthe air/actuation chamber (in the bottom plate 1100). The dimpledtexture on the dome of diaphragms 1226 provide, amongst other features,additional space for air and liquid to escape the chamber at the end ofstroke.

A system of the present invention may also include a balancing circuit,e.g., balancing circuit 143 as shown in FIG. 3A. In some cases, bloodflow circuit is implemented on a cassette, although it need not be.Within the balancing circuit, the flow of dialysate that passes in andout of the dialyzer may be balanced in some cases such that essentiallythe same amount of dialysate comes out of the dialyzer as goes into it(however, this balance can be altered in certain cases, due to the useof a bypass pump, as discussed below). In addition, in some cases, theflow of dialysate may also be balanced through the dialyzer such thatthe =the pressure of dialysate within the dialyzer generally equals thepressure of blood through the blood flow circuit.

A non-limiting example of a balancing circuit is shown in FIG. 5. Inbalancing circuit 143, dialysate flows from optional ultrafilter 73 intoone or more dialysate pumps 15 (e.g., two as shown in FIG. 5). Thedialysate pumps 15 in this figure include two pod pumps 161, 162, twobalancing chambers 341, 342, and pump 35 for bypassing the balancingchambers. The balancing chambers may be constructed such that they areformed from a rigid chamber with a flexible diaphragm dividing thechamber into two separate fluid compartments, so that entry of fluidinto one compartment can be used to force fluid out of the othercompartment and vice versa. Non-limiting examples of pumps that can beused as pod pumps and/or balancing chambers are described in U.S.Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14, 2006,entitled “Extracorporeal Thermal Therapy Systems and Methods”; or inU.S. Pat. No. 8,292,594, issued Oct. 23, 2012 and entitled “FluidPumping Systems, Devices and Methods,” each incorporated herein byreference. Additional examples of pod pumps are discussed in detailbelow. As can be seen in the schematic of FIG. 5, many of the valves canbe “ganged” or synchronized together in sets, so that all the valves ina set can be opened or closed at the same time.

More specifically, in one embodiment, balancing of flow works asfollows. FIG. 5 includes a first synchronized, controlled together setof valves 211, 212, 213, 241, 242, where valves 211, 212, 213 are gangedand valves 241 and 242 are ganged, as well as a second synchronized,controlled together set of valves 221, 222, 223, 231, 232, where valves221, 222, 223 are ganged, and valves 231 and 232 are ganged. At a firstpoint of time, the first ganged set of valves 211, 212, 213, 241, 242 isopened while the second ganged set of valves 221, 222, 223, 231, 232 isclosed. Fresh dialysate flows into balancing chamber 341 while useddialysate flows from dialyzer 14 into pod pump 161. Fresh dialysate doesnot flow into balancing chamber 342 since valve 221 is closed. As freshdialysate flows into balancing chamber 341, used dialysate withinbalancing chamber 341 is forced out and exits balancing circuit 143 (theused dialysate cannot enter pod pump 161 since valve 223 is closed).Simultaneously, pod pump 162 forces used dialysate present within thepod pump into balancing chamber 342 (through valve 213, which is open;valves 242 and 222 are closed, ensuring that the used dialysate flowsinto balancing chamber 342). This causes fresh dialysate containedwithin balancing chamber 342 to exit the balancing circuit 143 intodialyzer 14. Also, pod pump 161 draws in used dialysate from dialyzer 14into pod pump 161. This is also illustrated in FIG. 18A.

Once pod pump 161 and balancing chamber 341 have filled with dialysate,the first set of valves 211, 212, 213, 241, 242 is closed and the secondset of valves 221, 222, 223, 231, 232 is opened. Fresh dialysate flowsinto balancing chamber 342 instead of balancing chamber 341, as valve212 is closed while valve 221 is now open. As fresh dialysate flows intobalancing chamber 342, used dialysate within the chamber is forced outand exits balancing circuit, since valve 213 is now closed. Also, podpump 162 now draws used dialysate from the dialyzer into the pod pump,while used dialysate is prevented from flowing into pod pump 161 asvalve 232 is now closed and valve 222 is now open. Pod pump 161 forcesused dialysate contained within the pod pump (from the previous step)into balancing chamber 341, since valves 232 and 211 are closed andvalve 223 is open. This causes fresh dialysate contained withinbalancing chamber 341 to be directed into the dialyzer (since valve 241is now open while valve 212 is now closed). At the end of this step, podpump 162 and balancing chamber 342 have filled with dialysate. This putsthe state of the system back into the configuration at the beginning ofthis description, and the cycle is thus able to repeat, ensuring aconstant flow of dialysate to and from the dialyzer. This is alsoillustrated in FIG. 18B.

As a specific example, a vacuum (e.g., 4 p.s.i. of vacuum) can beapplied to the port for the first ganged set of valves, causing thosevalves to open, while positive pressure (e.g., 20 p.s.i. of airpressure, 1 p.s.i. is 6.89475 kilopascals) is applied to the secondganged set of valves, causing those valves to close (or vice versa). Thepod pumps each urge dialysate into one of the volumes in one of thebalancing chambers 341, 342. By forcing dialysate into a volume of abalancing chamber, an equal amount of dialysate is squeezed by thediaphragm out of the other volume in the balancing chamber. In eachbalancing chamber, one volume is occupied by fresh dialysate headingtowards the dialyzer and the other volume is occupied by used dialysateheading from the dialyzer. Thus, the volumes of dialysate entering andleaving the dialyzer are kept substantially equal.

As the diaphragms approach a wall in the balancing chambers (so that onevolume in a balancing chamber approaches a minimum and the other volumeapproaches a maximum), positive pressure is applied to the port for thefirst ganged set of valves, causing those valves to close, while avacuum is applied to the second ganged set of valves, causing thosevalves to open. The pod pumps then each urge dialysate into one of thevolumes in the other of the balancing chambers 341, 342. Again, byforcing dialysate into a volume of a balancing chamber, an equal amountof dialysate is squeezed by the diaphragm out of the other volume in thebalancing chamber. Since, in each balancing chamber, one volume isoccupied by fresh dialysate heading towards the dialyzer and the othervolume is occupied by used dialysate heading from the dialyzer, thevolumes of dialysate entering and leaving the dialyzer are kept equal.

Also shown within FIG. 5 is bypass pump 35, which can direct the flow ofdialysate from dialyzer 14 through balancing circuit 143 without passingthrough either of pod pumps 161 or 162. In this figure, bypass pump 35is a pod pump, similar to those described above, with a rigid chamberand a flexible diaphragm dividing each chamber into a fluid compartmentand a control compartment. This pump may be the same or different fromthe other pod pumps and/or balancing chambers described above. Forexample, this pump may be a pump as was described in U.S. ProvisionalPatent Application Ser. No. 60/792,073, filed Apr. 14, 2006, entitled“Extracorporeal Thermal Therapy Systems and Methods”; or in U.S. Pat.No. 8,292,594, issued Oct. 23, 2012 and entitled “Fluid Pumping Systems,Devices and Methods,” each incorporated herein by reference. Pod pumpsare also discussed in detail below.

When control fluid is used to actuate this pump, dialysate may be drawnthrough the dialyzer in a way that is not balanced with respect to theflow of blood through the dialyzer. This may cause the net flow ofliquid away from the patient, through the dialyzer, towards the drain.Such a bypass may be useful, for example, in reducing the amount offluid a patient has, which is often increased due to the patient'sinability to lose fluid (primarily water) through the kidneys. As shownin FIG. 5, bypass pump 35 may be controlled by a control fluid (e.g.,air), irrespective of the operation of pod pumps 161 and 162. Thisconfiguration may allow for easier control of net fluid removal from apatient, without the need to operate the balancing pumps in a way thatwould allow for such fluid to be withdrawn from the patient.

To achieve balanced flow across the dialyzer, the blood flow pump, thepumps of the balancing circuit, and the pumps of the directing circuit(discussed below) may be operated to work together to ensure that flowinto the dialyzer is generally equal to flow out of the dialyzer. Ifultrafiltration is required, the ultrafiltration pump (if one ispresent) may be run independently of some or all of the other bloodand/or dialysate pumps to achieve the desired ultrafiltration rate.

To prevent outgassing of the dialysate, the pumps of the balancingcircuit may be always kept at pressures above atmospheric pressure. Incontrast, however, the blood flow pump and the directing circuit pumpsuse pressures below atmosphere to pull the diaphragm towards the chamberwall for a fill stroke. Because of the potential of fluid transferacross the dialyzer and because the pumps of the balancing circuit runat positive pressures, the balancing circuit pumps may be able to useinformation from the blood flow pump(s) in order to run in a balancedflow mode.

In one set of embodiments, when running in such a balanced mode, ifthere is no delivery pressure from the blood flow pump, the balancingcircuit pump diaphragm will push fluid across the dialyzer into theblood and the alternate pod of the balancing circuit will not completelyfill. For this reason, the blood flow pump reports when it is activelydelivering a stroke. When the blood flow pump is delivering a stroke thebalancing pump operates. When the blood flow pump is not deliveringblood, the valves that control the flow from the dialyzer to thebalancing pumps (and other balancing valves ganged together with thesevalves, as previously discussed) may be closed to prevent any fluidtransfer from the blood side to the dialysate side from occurring.During the time the blood flow pump is not delivering, the balancingpumps are effectively frozen, and the stroke continues once the bloodflow pump starts delivering again. The balancing pump fill pressure canbe set to a minimal positive value to ensure that the pump operatesabove atmosphere at minimal impedance. Also, the balancing pump deliverypressure can be set to the blood flow pump pressure to generally matchpressures on either side of the dialyzer, minimizing flow across thedialyzer during delivery strokes of the inside pump.

It is generally beneficial to keep the blood flow as continuous aspossible during therapy, as stagnant blood flow can result in bloodclots. In addition, when the delivery flow rate on the blood flow pumpis discontinuous, the balancing pump must pause its stroke morefrequently, which can result in discontinuous and/or low dialysate flowrates.

However, the flow through the blood flow pump can be discontinuous forvarious reasons. For instance, pressure may be limited within the bloodflow pump, e.g., to +600 mmHg and/or −350 mmHg to provide safe pumpingpressures for the patient. For instance, during dual needle flow, thetwo pod pumps of the blood flow pump can be programmed to run 180° outof phase with one another. If there were no limits on pressure, thisphasing could always be achieved. However to provide safe blood flow forthe patient these pressures are limited. If the impedance is high on thefill stroke (due to a small needle, very viscous blood, poor patientaccess, etc.), the negative pressure limit may be reached and the fillflow rate will be slower then the desired fill flow rate. Thus thedelivery stroke must wait for the previous fill stroke to finishresulting in a pause in the delivery flow rate of the blood flow pump.Similarly, during single needle flow, the blood flow pump may be run at0° phase, where the two blood flow pump pod pumps are simultaneouslyemptied and filled. When both pod pumps are filled, the volumes of thetwo pod pumps are delivered. Thus the flow in single needle may bediscontinuous.

One method to control the pressure saturation limits would be to limitthe desired flow rate to the slowest of the fill and deliver strokes.Although this would result in slower blood delivery flow rates, the flowrate would still be known and would always be continuous which wouldresult in more accurate and continuous dialysate flow rates. Anothermethod to make the blood flow rate more continuous in single needleoperation would be to use maximum pressures to fill the pods so the filltime would be minimized. The desired deliver time could then be set tobe the total desired stroke time minus the time that the fill stroketook. However, if blood flow rate cannot be made continuous, thendialysate flow rate may have to be adjusted so that when the blood flowrate is delivering the dialysate flow is higher then the programmedvalue to make up for the time that the dialysate pump is stopped whenthe blood flow pump is filling. If this is done with the correct timing,an average dialysate flow rate taken over several strokes can stillmatch the desired dialysate flow rate.

A non-limiting example of a balancing cassette is shown in FIGS. 34-36.In one structure of the cassette shown in FIG. 34A, the valves areganged such that they are actuated at the same time. In one embodiment,there are four gangs of valves 832, 834, 836, 838. In some cases, theganged valves are actuated by the same air line. However, in otherembodiments, each valve has its own air line. Ganging the valves asshown in the exemplary embodiment creates the fluid-flow describedabove. In some embodiments, ganging the valves also ensures theappropriate valves are opened and closed to dictate the fluid pathwaysas desired.

In this embodiment, the fluid valves are volcano valves, as described inmore detail herein. Although the fluid flow-path schematic has beendescribed with respect to a particular flow path, in variousembodiments, the flow paths may change based on the actuation of thevalves and the pumps. Additionally, the terms inlet and outlet as wellas first fluid and second fluid are used for description purposes only(for this cassette, and other cassettes described herein as well). Inother embodiments, an inlet can be an outlet, as well as, a first andsecond fluid may be different fluids or the same fluid types orcomposition.

Referring now to FIGS. 35A-35E, the top plate 1000 of an exemplaryembodiment of the cassette is shown. Referring first to FIGS. 35A and35B, the top view of the top plate 1000 is shown. In this exemplaryembodiment, the pod pumps 820, 828 and the balancing pods 812, 822 onthe top plate, are formed in a similar fashion. In this embodiment, thepod pumps 820, 828 and balancing pods 812, 822, when assembled with thebottom plate, have a total volume of capacity of 38 ml. However, invarious embodiments, the total volume capacity can be greater or lessthan in this embodiment. The first fluid inlet 810 and the second fluidoutlet 816 are shown.

Referring now to FIGS. 35C and 35D, the bottom view of the top plate1000 is shown. The fluid paths are shown in this view. These fluid pathscorrespond to the fluid paths shown in FIG. 34B in the midplate 900. Thetop plate 1000 and the top of the midplate form the liquid or fluid sideof the cassette for the pod pumps 820, 828 and for one side of thebalancing pods 812, 822. Thus, most of the liquid flow paths are on thetop and midplates. The other side of the balancing pods' 812, 822 flowpaths are located on the inner side of the bottom plate, not shown here,shown in FIGS. 36A-36B.

Still referring to FIGS. 35C and 35D, the pod pumps 820, 828 andbalancing pods 812, 822 include a groove 1002. The groove 1002 is shownhaving a particular shape, however, in other embodiments, the shape ofthe groove 1002 can be any shape desirable. The shape shown in FIGS. 35Cand 35D is an exemplary embodiment. In some embodiments of the groove1002, the groove forms a path between the fluid inlet side and the fluidoutlet side of the pod pumps 820, 828 and balancing pods 812, 822.

The groove 1002 provides a fluid path whereby when the diaphragm is atthe end of stroke, there is still a fluid path between the inlet andoutlet such that the pockets of fluid or air do not get trapped in thepod pump or balancing pod. The groove 1002 is included in both theliquid and air sides of the pod pumps 820, 828 and balancing pods 812,822 (see FIGS. 36A-36B with respect to the air side of the pod pumps820, 828 and the opposite side of the balancing pods 812, 822).

The liquid side of the pod pumps 820, 828 and balancing pods 812, 822,in one exemplary embodiment, include a feature whereby the inlet andoutlet flow paths are continuous while the outer ring 1004 is alsocontinuous. This feature allows for the seal, formed with the diaphragm(not shown) to be maintained.

Referring to FIG. 35E, the side view of an exemplary embodiment of thetop plate 1000 is shown. The continuous outer ring 1004 of the pod pumps820, 828 and balancing pods 812, 822 can be seen.

Referring now to FIGS. 36A-36E, the bottom plate 1100 is shown.Referring first to FIGS. 36A and 36B, the inside surface of the bottomplate 1100 is shown. The inside surface is the side that contacts thebottom surface of the midplate (not shown, see FIG. 34E). The bottomplate 1100 attaches to the air lines (not shown). The correspondingentrance holes for the air that actuates the pod pumps 820, 928 andvalves (not shown, see FIG. 34E) in the midplate can be seen 1106. Holes1108, 1110 correspond to the second fluid inlet and second fluid outletshown in FIGS. 34C, 824, 826 respectively. The corresponding halves ofthe pod pumps 820, 828 and balancing pods 812, 822 are also shown, asare the grooves 1112 for the fluid paths. Unlike the top plate, thebottom plate corresponding halves of the pod pumps 820, 828 andbalancing pods 812, 822 make apparent the difference between the podpumps 820, 828 and balancing pods 812, 822. The pod pumps 820, 828include an air path on the second half in the bottom plate, while thebalancing pods 812, 822 have identical construction to the half in thetop plate. Again, the balancing pods 812, 822 balance liquid, thus, bothsides of the diaphragm, not shown, will include a liquid fluid path,while the pod pumps 820, 828 are pressure pumps that pump liquid, thus,one side includes a liquid fluid path and the other side, shown in thebottom plate 1100, includes an air actuation chamber or air fluid path.

In one exemplary embodiment of the cassette, sensor elements areincorporated into the cassette so as to discern various properties ofthe fluid being pumped. In one embodiment, the three sensor elements areincluded. In one embodiment, the sensor elements are located in thesensor cell 1114. The cell 1114 accommodates three sensor elements inthe sensor element housings 1116, 1118, 1120. In an embodiment, two ofthe sensor housings 1116, 1118 accommodate a conductivity sensor elementand the third sensor element housing 1120 accommodates a temperaturesensor element. The conductivity sensor elements and temperature sensorelements can be any conductivity or temperature sensor elements in theart. In one embodiment, the conductivity sensor elements are graphiteposts. In other embodiments, the conductivity sensor elements are postsmade from stainless steel, titanium, platinum or any other metal coatedto be corrosion resistant and still be electrically conductive. Theconductivity sensor elements can include an electrical lead thattransmits the probe information to a controller or other device. In oneembodiment, the temperature sensor is a thermister potted in a stainlesssteel probe. In alternate embodiments, there are either no sensors inthe cassette or only a temperature sensor, only one or more conductivitysensors or one or more of another type of sensor. In some embodiments,the sensor elements are located outside of the cassette, in a separatecassette, and may be connected to the cassette via a fluid line.

Still referring to FIGS. 36A and 36B, the actuation side of the meteringpump 830 is also shown as well as the corresponding air entrance hole1106 for the air that actuates the pump. Referring now to FIGS. 36C and36D, the outer side of the bottom plate 1100 is shown. The valve, podpumps 820, 828 and metering pump 830 air line connection points 1122 areshown. Again, the balancing pods 812, 822 do not have air lineconnection points as they are not actuated by air. As well, thecorresponding openings in the bottom plate 1100 for the second fluidoutlet 824 and second fluid inlet 826 are shown.

Referring now to FIG. 36E, a side view of the bottom plate 1100 isshown. In the side view, the rim 1124 that surrounds the inner bottomplate 1100 can be seen. The rim 1124 is raised and continuous, providingfor a connect point for the diaphragm (not shown). The diaphragm restson this continuous and raised rim 1124 providing for a seal between thehalf of the pod pumps 820, 828 and balancing pods 812, 822 in the bottomplate 1100 and the half of the pod pumps 820, 828 and balancing pods812, 822 in the top plate (not shown, see FIGS. 35A-35D).

As mentioned, dialysate flows from a directing circuit, optionallythrough a heater and/or through an ultrafilter, to the balancingcircuit. In some cases, the directing circuit is implemented on acassette, although it need not be. An example of a directing circuit canbe seen in FIG. 3A as directing circuit 142. Directing circuit 142 isable to perform a number of different functions, in this example. Forinstance, dialysate flows from a dialysate supply (such as from a mixingcircuit, as discussed below) through the directing circuit to abalancing circuit, while used dialysate flows from the balancing circuitto a drain. The dialysate may flow due to the operation of one or morepumps contained within the directing circuit. In some cases, thedirecting circuit may also contain a dialysate tank, which may containdialysate prior to passing the dialysate to the balancing circuit. Sucha dialysate tank, in certain instances, may allow the rate of productionof dialysate to be different than the rate of use of dialysate in thedialyzer within the system. The directing circuit may also direct waterfrom a water supply to the mixing circuit (if one is present). Inaddition, as previously discussed, the blood flow circuit may befluidically connected to the directing circuit for some operations,e.g., disinfection.

Thus, in some cases, dialysate may be made as it is needed, so thatlarge volumes of dialysate do not need to be stored. For instance, afterthe dialysate is prepared, it may be held in a dialysate tank 169. Adialysate valve 17 may control the flow of dialysate from tank 169 intothe dialysate circuit 20. The dialysate may be filtered and/or heatedbefore being sent into the dialyzer 14. A waste valve 18 may be used tocontrol the flow of used dialysate out of the dialysate circuit 20.

One non-limiting example of a directing circuit is shown in FIG. 6. Inthis figure, directing circuit 142 fluidically connects dialysate from adialysate supply to a dialysate tank 169, then through dialysate pump159, heater 72, and ultrafilter 73, before entering a balancing circuit,as previously discussed. It should be understood that although thisfigure shows that dialysate in the dialysate flow path flows from thedialysate supply to the dialysate tank, the pump, the heater, and theultrafilter (in that order), other orderings are also possible in otherembodiments. Heater 72 may be used to warm the dialysate to bodytemperature, and/or a temperature such that the blood in the blood flowcircuit is heated by the dialysate, and the blood returning to thepatient is at body temperature. Ultrafilter 73 may be used to remove anypathogens, pyrogens, etc. which may be in the dialysate solution, asdiscussed below. The dialysate solution then flows into the balancingcircuit to be directed to the dialyzer.

Dialysate tank 169 may comprise any suitable material and be of anysuitable dimension for storing dialysate prior to use. For instance,dialysate tank 169 may comprise plastic, metal, etc. In some cases,dialysate tank may comprise materials similar to those used to form thepod pumps as discussed herein.

The flow of dialysate through directing circuit 142 may be controlled(at least in part) by operation of dialysate pump 159. In addition,dialysate pump 159 may control flow through the balancing circuit. Forinstance, as discussed above with reference to FIG. 5, fresh dialysatefrom the directing circuit flows into balancing chambers 341 and 342 onbalancing circuit 143; pump 159 may be used as a driving force to causethe fresh dialysate to flow into these balancing chambers. In one set ofembodiments, dialysate pump 159 includes a pod pump, similar to thosedescribed above. The pod pump may include a rigid chamber with aflexible diaphragm dividing each chamber into a fluid compartment andcontrol compartment. The control compartment may be connected to acontrol fluid source, such as an air source. Non-limiting examples ofpumps that may be used as pod pumps and/or balancing chambers aredescribed in U.S. Provisional Patent Application Ser. No. 60/792,073,filed Apr. 14, 2006, entitled “Extracorporeal Thermal Therapy Systemsand Methods”; or in U.S. Pat. No. 8,292,594, issued Oct. 23, 2012 andentitled “Fluid Pumping Systems, Devices and Methods,” each incorporatedherein by reference. Pod pumps are also discussed in detail below.

After passing through pump 159, the dialysate may flow to a heater,e.g., heater 72 in FIG. 6. The heater may be any heating device suitablefor heating dialysate, for example, an electrically resistive heater asis known to those of ordinary skill in the art. The heater may be keptseparated from the directing circuit (e.g., as is shown in FIG. 3A), orthe heater may be incorporated into the directing circuit, or othercircuits as well (e.g., the balancing circuit).

In some cases, the dialysate is heated to a temperature such that bloodpassing through the dialyzer is not significantly chilled. For instance,the temperature of the dialysate may be controlled such that thedialysate is at a temperature at or greater than the temperature of theblood passing through the dialyzer. In such an example, the blood may beheated somewhat, which may be useful in offsetting heat loss caused bythe blood passing through the various components of the blood flowcircuit, as discussed above. In addition, in some cases as discussedbelow, the heater may be connected to a control system such thatdialysate that is incorrectly heated (i.e., the dialysate is too hot ortoo cold) may be recycled (e.g., back to the dialysate tank) instead ofbeing passed to the dialyzer, for example, via line 731. The heater maybe integrated as part of a fluid circuit, such as a directing circuitand/or a balancing circuit, or, as is shown in FIG. 3A, the heater maybe a separate component within the dialysate flow path.

The heater may also be used, in some embodiments, for disinfection orsterilization purposes. For instance, water may be passed through thehemodialysis system and heated using the heater such that the water isheated to a temperature able to cause disinfection or sterilization tooccur, e.g., temperatures of at least about 70° C., at least about 80°C., at least about 90° C., at least about 100° C., at least about 110°C., etc. In some cases, as discussed below, the water may be recycledaround the various components and/or heat loss within the system may beminimized (e.g., as discussed below) such that the heater is able toheat the water to such disinfection or sterilization temperatures.

The heater may include a control system that is able to control theheater as discussed above (e.g., to bring dialysate up to bodytemperature for dialyzing a patient, to bring the water temperature upto a disinfection temperatures in order to clean the system, etc.).

A non-limiting example of a heater controller follows. The controllermay be selected to be capable of dealing with varying inlet fluidtemperatures as well as for pulsatile or varying flow rates. In additionthe heater control must function properly when flow is directed througheach of the different flow paths (dialyze, disinfect, re-circulate etc).In one embodiment, the heater controller is used on SIP1 boards with anIR (infrared) temperature sensor on the ultra filter and an IRtemperature sensor on the tank. In other embodiments, the board is in abox with less heat losses and to uses conductivity sensors for the inlettemperature sensor. Another embodiment of the controller uses a simpleproportional controller using both tank (heater inlet) and ultrafilter(heater outlet) temperatures, e.g.:powerHeater=massFlow*((tankPGain*errorTank)+(UFPGain*errorUF),where:

PowerHeater=heater duty cycle cmd (0-100%);

MassFlow=the fluid mass flow rate;

TankPGain=proportional gain for the tank or inlet temperature sensor;

ErrorTank=difference between the tank or inlet temperature sensor andthe desired temperature;

UFPGain=proportional gain for the ultrafilter or outlet temperaturesensor; and

ErrorUF=difference between the of or outlet temperature sensor and thedesired temperature.

From the heater duty cycle command (0-100%) a PWM command is generated.In some embodiments, this controller may reduce the mass flow rate ifthe given temperature is not maintained and the heater is saturated.

It should be understood that the above-described heater control is byway of example only, and that other heater control systems, and otherheaters, are also possible in other embodiments of the invention.

The dialysate may also be filtered to remove contaminants, infectiousorganisms, pathogens, pyrogens, debris, and the like, for instance,using an ultrafilter. The filter may be positioned in any suitablelocation in the dialysate flow path, for instance, between the directingcircuit and the balancing circuit, e.g., as is shown in FIG. 3A, and/orthe ultrafilter may be incorporated into the directing circuit or thebalancing circuit. If an ultrafilter is used, it may be chosen to have amesh size chosen to prevent species such as these from through thefilter. For instance, the mesh size may be less than about 0.3micrometers, less than about 0.2 micrometers, less than about 0.1micrometers, or less than about 0.05 micrometers, etc. Those of ordinaryskill in the art will be aware of filters such as ultrafilters, and inmany cases, such filters may be readily obtained commercially.

In some cases, the ultrafilter may be operated such that waste from thefilter (e.g., the retentate stream) is passed to a waste stream, such aswaste line 39 in FIG. 6. In some cases, the amount of dialysate flowinginto the retentate stream may be controlled. For instance, if theretentate is too cold (i.e., heater 72 is not working, or heater 72 isnot heating the dialysate to a sufficient temperature, the entiredialysate stream (or at least a portion of the dialysate) may bediverted to waste line 39, and optionally, recycled to dialysate tank169 using line 48. Flow from the filter may also be monitored forseveral reasons, e.g., using temperature sensors (e.g., sensors 251 and252), conductivity sensors (for confirming dialysate concentration,e.g., sensor 253), or the like. An example of such sensors is discussedbelow; further non-limiting examples can be seen in U.S. Pat. No.8,491,184, issued Jul. 23, 2013, entitled “Sensor Apparatus Systems,Devices and Methods,” incorporated herein by reference.

It should be noted that the ultrafilter and the dialyzer provideredundant screening methods for the removal of contaminants, infectiousorganisms, pathogens, pyrogens, debris, and the like, in this particularexample (although in other cases, the ultrafilter may be absent).Accordingly, for contaminants to reach the patient from the dialysate,the contaminants must pass through both the ultrafilter and thedialyzer. Even in the event that one fails, the other may still be ableto provide sterility and prevent contaminants from reaching thepatient's blood.

Directing circuit 142 may also be able to route used dialysate comingfrom a balancing circuit to a drain, e.g., through waste line 39 todrain 31 in FIG. 6. The drain may be, for example, a municipal drain ora separate container for containing the waste (e.g., used dialysate) tobe properly disposed of. In some cases, one or more check or “one-way”valves (e.g., check valves 215 and 216) may be used to control flow ofwaste from the directing circuit and from the system. Also, in certaininstances, a blood leak sensor (e.g., sensor 258) may be used todetermine if blood is leaking through the dialyzer into the dialysateflow path.

In addition, directing circuit 142 may receive water from a water supply30, e.g., from a container of water such as a bag, and/or from a deviceable to produce water, e.g., a reverse osmosis device such as those thatare commercially available. In some cases, as is known to those ofordinary skill in the art, the water entering the system is set at acertain purity, e.g., having ion concentrations below certain values.The water entering directing circuit 142 may be passed on to variouslocations, e.g., to a mixing circuit for producing fresh dialysateand/or to waste line 39. In some cases, as discussed below, valves todrain 31, various recycle lines are opened, and conduits 67 may beconnected between directing circuit 142 and blood flow circuit 141, suchthat water is able to flow continuously around the system. If heater 72is also activated, the water passing through the system will becontinuously heated, e.g., to a temperature sufficient to disinfect thesystem. Such disinfection methods will be discussed in detail below.

A non-limiting example of a directing cassette is shown in FIGS. 41-45.Referring now to FIGS. 41A and 41B, the outer side of the top plate 900of one embodiment of the cassette is shown. The top plate 900 includesone half of the pod pumps 820, 828. This half is the fluid/liquid halfwhere the source fluid will flow through. The inlet and outlet pod pumpfluid paths are shown. These fluid paths lead to their respective podpumps 820, 828.

The pod pumps 820, 828 can include a raised flow path 908, 910. Theraised flow path 908, 910 allows for the fluid to continue to flowthrough the pod pumps 820, 828 after the diaphragm (not shown) reachesthe end of stroke. Thus, the raised flow path 908, 910 minimizes thediaphragm causing air or fluid to be trapped in the pod pump 820, 828 orthe diaphragm blocking the inlet or outlet of the pod pump 820, 828,which would inhibit flow. The raised flow path 908, 910 is shown in thisembodiment having particular dimensions. In alternate embodiments, theraised flow path 908, 910 is larger or narrower, or in still otherembodiments, the raised flow path 908, 910 can be any dimension as thepurpose is to control fluid flow so as to achieve a desired flow rate orbehavior of the fluid. Thus, the dimensions shown and described herewith respect to the raised flow path, the pod pumps, the valves, or anyother aspect are mere exemplary and alternate embodiments. Otherembodiments are readily apparent. FIGS. 41C and 41D show the inner sideof the top plate 900 of this embodiment of the cassette. FIG. 41E showsa side view of the top plate 900.

Referring now to FIGS. 42A and 42B, the fluid/liquid side of themidplate 1000 is shown. The areas complementary to the fluid paths onthe inner top plate shown in FIGS. 41C and 41D are shown. These areasare slightly raised tracks that present a surface finish that isconducive to laser welding, which is one mode of manufacturing in thisembodiment. Other modes of manufacturing the cassette are discussedabove.

Referring next to FIGS. 42C and 42D, the air side, or side facing thebottom plate (not shown, shown in FIGS. 43A-43E) of the midplate 1000 isshown according to this embodiment. The air side of the valve holes 802,808, 814, 816, 822, 836, 838, 840, 842, 844, 856 correspond to the holesin the fluid side of the midplate 1000 (shown in FIGS. 42A and 42B). Asseen in FIGS. 44C and 44D, diaphragms 1220 complete pod pumps 820, 828while diaphragms 1222 complete valves 802, 808, 814, 816, 822, 836, 838,840, 842, 844, 856. The valves 802, 808, 814, 816, 822, 836, 838, 840,842, 844, 856 are actuated pneumatically, and as the diaphragm is pulledaway from the holes, liquid/fluid is allowed to flow. As the diaphragmis pushed toward the holes, fluid flow is inhibited. The fluid flow isdirected by the opening and closing of the valves 802, 808, 814, 816,822, 836, 838, 840, 842, 844, 856. Referring next to FIGS. 43A and 43B,the inner view of the bottom plate 1100 is shown. The inside view of thepod pumps 820, 828, and the valves 802, 808, 814, 816, 822, 836, 838,840, 842, 844, 856 actuation/air chamber is shown. The pod pumps 820,828, and the valves 802, 808, 814, 816, 822, 836, 838, 840, 842, 844,856 are actuated by a pneumatic air source. Referring now to FIGS. 43Cand 43D, the outer side of the bottom plate 1100 is shown. The source ofair is attached to this side of the cassette. In one embodiment, tubesconnect to the tubes on the valves and pumps 1102. In some embodiments,the valves are ganged, and more than one valve is actuated by the sameair line.

Referring now to FIGS. 44A and 44B, an assembled cassette 1200 is shown.An exploded view of the assembled cassette 1200 shown in FIGS. 44A and44B is shown in FIGS. 12C and 12D. In these views, the embodiment of thepod pump diaphragms 1220 is shown. The gasket of the diaphragm providesa seal between the liquid chamber (in the top plate 900) and theair/actuation chamber (in the bottom plate 1100). In some embodiment,texture on the dome of the diaphragms 1220 provide, amongst otherfeatures, additional space for air and liquid to escape the chamber atthe end of stroke. In alternate embodiments of the cassette, thediaphragms may include a double gasket. The double gasket feature wouldbe preferred in embodiments where both sides of the pod pump includeliquid or in applications where sealing both chambers' sides is desired.In these embodiments, a rim complementary to the gasket or other feature(not shown) would be added to the inner bottom plate 1100 for the gasketto seal the pod pump chamber in the bottom plate 1100.

Referring now to FIG. 45, a cross sectional view of the pod pumps 828 inthe cassette is shown. The details of the attachment of the diaphragm1220 can be seen in this view. Again, in this embodiment, the diaphragm1220 gasket is pinched by the midplate 1000 and the bottom plate 1100. Arim on the midplate 1000 provides a feature for the gasket to seal thepod pump 828 chamber located in the top plate 900.

Referring next to FIG. 45, this cross sectional view shows the valves834, 836 in the assembled cassette. The diaphragms 1220 are shownassembled and are held in place, in this embodiment, by being sandwichedbetween the midplate 1000 and the bottom plate 1100. Still referring toFIG. 45, this cross sectional view also shows a valve 822 in theassembled cassette. The diaphragm 1222 is shown held in place by beingsandwiched between the midplate 1000 and the bottom plate 1100.

In one set of embodiments, dialysate may be prepared separately andbrought to the system for use in the directing circuit. However, in somecases, dialysate may be prepared in a mixing circuit. The mixing circuitmay be run to produce dialysate at any suitable time. For instance,dialysate may be produced during dialysis of a patient, and/or prior todialysis (the dialysate may be stored, for instance, in a dialysatetank. Within the mixing circuit, water (e.g., from a water supply,optionally delivered to the mixing circuit by a directing circuit) maybe mixed with various dialysate ingredients to form the dialysate. Thoseof ordinary skill in the art will know of suitable dialysateingredients, for instance, sodium bicarbonate, sodium chloride, and/oracid, as previously discussed. The dialysate may be constituted on anas-needed basis, so that large quantities do not need to be stored,although some may be stored within a dialysate tank, in certain cases.

FIG. 7A illustrates a non-limiting example of a mixing circuit, whichmay be implemented on a cassette in some cases. In FIG. 7A, water from adirecting circuit flows into mixing circuit 25 due to action of pump180. In some cases, a portion of the water is directed to ingredients49, e.g., for use in transporting the ingredients through the mixingcircuit. As shown in FIG. 7A, water is delivered to bicarbonate source28 (which may also contain sodium chloride in some cases). The sodiumchloride and/or the sodium bicarbonate may be provided, in some cases,in a powdered or granular form, which is moved through the action ofwater. Bicarbonate from bicarbonate source 28 is delivered viabicarbonate pump 183 to a mixing line 186, to which water from thedirecting circuit also flows. Acid from acid source 29 (which may be ina liquid form) is also pumped via acid pump 184 to mixing line 186. Theingredients (water, bicarbonate, acid, NaCl, etc.) are mixed in mixingchamber 189 to produce dialysate, which then flows out of mixing circuit25. Conductivity sensors 178 and 179 are positioned along mixing line186 to ensure that as each ingredient is added to the mixing line, it isadded at proper concentrations.

In one set of embodiments, pump 180 comprises one or more pod pumps,similar to those described above. The pod pumps may include a rigidchamber with a flexible diaphragm dividing each chamber into a fluidcompartment and control compartment. The control compartment may beconnected to a control fluid source, such as an air source. Non-limitingexamples of pumps that can be used as pod pumps are described in U.S.Provisional Patent Application Ser. No. 60/792,073, filed Apr. 14, 2006,entitled “Extracorporeal Thermal Therapy Systems and Methods”; or inU.S. Pat. No. 8,292,594, issued Oct. 23, 2012 and entitled “FluidPumping Systems, Devices and Methods,” each incorporated herein byreference. Similarly, in some cases, pumps 183 and/or 184 may each bepod pumps. Additional details of pod pumps are discussed below.

In some cases, one or more of the pumps may have pressure sensors tomonitor the pressure in the pump. This pressure sensor may be used toensure that a pump compartment is filling and delivering completely. Forexample, ensuring that the pump delivers a full stroke of fluid may beaccomplished by (i) filling the compartment, (ii) closing both fluidvalves, (iii) applying pressure to the compartment by opening the valvebetween the positive pneumatic reservoir and the compartment, (iv)closing this positive pressure valve, leaving pressurized air in thepath between the valve and the compartment, (v) opening the fluid valveso the fluid can leave the pump compartment, and (vi) monitoring thepressure drop in the compartment as the fluid leaves. The pressure dropcorresponding to a full stroke may be consistent, and may depend on theinitial pressure, the hold-up volume between the valve and thecompartment, and/or the stroke volume. However, in other embodiments ofany of the pod pumps described herein, a reference volume compartmentmay be used, where the volume is determined through pressure and volumedata.

The volumes delivered by the water pump and/or the other pumps may bedirectly related to the conductivity measurements, so the volumetricmeasurements may be used as a cross-check on the composition of thedialysate that is produced. This may ensure that the dialysatecomposition remains safe even if a conductivity measurement becomesinaccurate during a therapy.

FIG. 7B is a schematic diagram showing another example of a mixingcircuit, implementable on a cassette in certain cases. Mixing circuit 25in this figure includes a pod pump 181 for pumping water from a supplyalong a line 186 into which the various ingredients for making thedialysate are introduced into the water. Another pump 182 pumps waterfrom a water supply into source 28 holding the sodium bicarbonate (e.g.,a container) and/or into source 188 holding the sodium chloride. A thirdpump 183 introduces the dissolved bicarbonate into mixing line 186(mixed in mixing chamber 189), while a fourth pump 185 introducesdissolved sodium chloride into line 186 (mixed in mixing chamber 191). Afifth pump 184 introduces acid into the water before it passes throughthe first pump 181. Mixing is monitored using conductivity sensors 178,179, and 177, which each measure the conductivity after a specificingredient has been added to mixing line 186, to ensure that the properamount and/or concentration of the ingredient has been added. An exampleof such sensors is discussed below; further non-limiting examples can beseen in U.S. Pat. No. 8,491,184, issued Jul. 23, 2013, entitled “SensorApparatus Systems, Devices and Methods,” incorporated herein byreference.

Referring now to FIG. 3B, in this embodiment, mixing circuit 25constitutes dialysate using two sources: an acid concentrate source 27and a combined sodium bicarbonate (NaHCO₃) and sodium chloride (NaCl)source. As shown in the embodiment shown in FIG. 3B, in someembodiments, the dialysate constituting system 25 may include multiplesof each source. In embodiments of the method where the system is runcontinuously, the redundant dialysate sources allow for continuousfunction of the system, as one set of sources is depleted, the systemuses the redundant source and the first set of sources is replaced. Thisprocess is repeated as necessary, e.g., until the system is shut down.

A non-limiting example of a balancing cassette is shown in FIGS. 34-36.In the exemplary fluid flow-path cassette shown in FIG. 37, valves areopen individually. In this exemplary embodiment, the valves arepneumatically open. Also, in this embodiment, the fluid valves arevolcano valves, as described in more detail elsewhere in thisspecification.

Referring now to FIGS. 38A-38B, the top plate 1100 of one exemplaryembodiment of the cassette is shown. In this exemplary embodiment, thepod pumps 820, 828 and the mixing chambers 818 on the top plate 1100,are formed in a similar fashion. In this exemplary embodiment, the podpumps 820, 828 and mixing chamber 818, when assembled with the bottomplate, have a total volume of capacity of 38 ml. However, in otherembodiments, the mixing chamber may have any size volume desired.

Referring now to FIG. 38B, the bottom view of the top plate 1100 isshown. The fluid paths are shown in this view. These fluid pathscorrespond to the fluid paths shown in FIGS. 39A-39B in the midplate1200. The top plate 1100 and the top of the midplate 1200 form theliquid or fluid side of the cassette for the pod pumps 820, 828 and forone side of the mixing chamber 818. Thus, most of the liquid flow pathsare on the top 1100 and midplates 1200. Referring to FIG. 39B, the firstfluid inlet 810 and the first fluid outlet 824 are shown.

Still referring to FIGS. 38A and 38B, the pod pumps 820, 828 include agroove 1002 (in alternate embodiments, this is a groove). The groove1002 is shown having a particular size and shape, however, in otherembodiments, the size and shape of the groove 1002 may be any size orshape desirable. The size and shape shown in FIGS. 38A and 38B is oneexemplary embodiment. In all embodiments of the groove 1002, the groove1002 forms a path between the fluid inlet side and the fluid outlet sideof the pod pumps 820, 828. In alternate embodiments, the groove 1002 isa groove in the inner pumping chamber wall of the pod pump.

The groove 1002 provides a fluid path whereby when the diaphragm is atthe end-of-stroke there is still a fluid path between the inlet andoutlet such that the pockets of fluid or air do not get trapped in thepod pump. The groove 1002 is included in both the liquid/fluid andair/actuation sides of the pod pumps 820, 828. In some embodiments, thegroove 1002 may also be included in the mixing chamber 818 (see FIGS.40A-40B with respect to the actuation/air side of the pod pumps 820, 828and the opposite side of the mixing chamber 818. In alternateembodiments, the groove 1002 is either not included or on only one sideof the pod pumps 820, 828.

In an alternate embodiment of the cassette, the liquid/fluid side of thepod pumps 820, 828 may include a feature (not shown) whereby the inletand outlet flow paths are continuous and a rigid outer ring (not shown)is molded about the circumference of the pumping chamber is alsocontinuous. This feature allows for the seal, formed with the diaphragm(not shown) to be maintained. Referring to FIG. 38E, the side view of anexemplary embodiment of the top plate 1100 is shown.

Referring now to FIGS. 39A-39B, an exemplary embodiment of the midplate1200 is shown. The midplate 1200 is also shown in FIGS. 37A-37F, wherethese Figs. correspond with FIGS. 39A-39B. Thus, FIGS. 37A-37F indicatethe locations of the various valves and valving paths. The locations ofthe diaphragms (not shown) for the respective pod pumps 820, 828 as wellas the location of the mixing chamber 818 are shown.

Referring now to FIG. 39A, in one exemplary embodiment of the cassette,sensor elements are incorporated into the cassette so as to discernvarious properties of the fluid being pumped. In one embodiment, threesensor elements are included. However, in this embodiment, six sensorelements (two sets of three) are included. The sensor elements arelocated in the sensor cell 1314, 1316. In this embodiment, a sensor cell1314, 1316 is included as an area on the cassette for sensor(s)elements. In one embodiment, the three sensor elements of the two sensorcells 1314, 1316 are housed in respective sensor elements housings 1308,1310, 1312 and 1318, 1320, 1322. In one embodiment, two of the sensorelements housings 1308, 1312 and 1318, 1320 accommodate a conductivitysensor elements and the third sensor elements housing 1310, 1322accommodates a temperature sensor elements. The conductivity sensorelements and temperature sensor elements may be any conductivity ortemperature sensor elements in the art. In one embodiment, theconductivity sensors are graphite posts. In other embodiments, theconductivity sensor elements are posts made from stainless steel,titanium, platinum or any other metal coated to be corrosion resistantand still be electrically conductive. The conductivity sensor elementswill include an electrical lead that transmits the probe information toa controller or other device. In one embodiment, the temperature sensoris a thermister potted in a stainless steel probe. However, in alternateembodiments, a combination temperature and conductivity sensor elementsis used similar to the one described in a U.S. Patent ApplicationPublication No. US 2008-0240929, published Oct. 2, 2008, entitled“Sensor Apparatus Systems, Devices and Methods.”

In alternate embodiments, there are either no sensors in the cassette oronly a temperature sensor, only one or more conductivity sensors or oneor more of another type of sensor.

Referring now to FIG. 39C, the side view of an exemplary embodiment ofthe midplate 1200 is shown. Referring now to FIGS. 40A-40B, the bottomplate 1300 is shown. Referring first to FIG. 40A, the inner or insidesurface of the bottom plate 1300 is shown. The inner or inside surfaceis the side that contacts the bottom surface of the midplate (notshown). The bottom plate 1300 attaches to the air or actuation lines(not shown). The corresponding entrance holes for the air that actuatesthe pod pumps 820, 828 and valves (not shown, see FIGS. 37A-37F) in themidplate 1300 can be seen. Holes 810, 824 correspond to the first fluidinlet and first fluid outlet shown in FIGS. 39B, 810, 824 respectively.The corresponding halves of the pod pumps 820, 828 and mixing chamber818 are also shown, as are the grooves 1002 for the fluid paths. Theactuation holes in the pumps are also shown. Unlike the top plate, thebottom plate 1300 corresponding halves of the pod pumps 820, 828 andmixing chamber 818 make apparent the difference between the pod pumps820, 828 and mixing chamber 818. The pod pumps 820, 828 include anair/actuation path on the bottom plate 1300, while the mixing chamber818 has identical construction to the half in the top plate. The mixingchamber 818 mixes liquid and therefore, does not include a diaphragm(not shown) nor an air/actuation path. The sensor cell 1314, 1316 withthe three sensor element housings 1308, 1310, 1312 and 1318, 1320, 1322are also shown.

Referring now to FIG. 40B, the actuation ports 1306 are shown on theoutside or outer bottom plate 1300. An actuation source is connected tothese actuation ports 1306. Again, the mixing chamber 818 does not havean actuation port as it is not actuated by air. Referring to FIG. 40C, aside view of the exemplary embodiment of the bottom plate 1300 is shown.

As described above, in various aspects of the invention, one or morefluid circuits may be implemented on a cassette, such as the blood flowcircuit, the balancing circuit, the directing circuit, and/or the mixingcircuit, etc. Other cassettes may be present, e.g., a sensing cassetteas is disclosed in U.S. Pat. No. 8,491,184, issued Jul. 23, 2013,entitled “Sensor Apparatus Systems, Devices and Methods,” incorporatedherein by reference. In some embodiments, some or all of these circuitsare combined in a single cassette. In alternate embodiments, thesecircuits are each defined in respective cassettes. In still otherembodiments, two or more of the fluid circuits are included on onecassette. In some cases, two, three, or more cassettes may beimmobilized relative to each other, optionally with fluidic connectionsbetween the cassettes. For instance, in one embodiment, two cassettesmay be connected via a pump, such as a pod pump as previously described.The pod pump may include a rigid chamber with a flexible diaphragmdividing each chamber into a first side and a second side, and the sidesmay be used for various purposes as noted above.

Non-limiting examples of cassettes that may be used in the presentinvention include those described in U.S. patent application Ser. No.11/871,680, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,712, filed Oct. 12, 2007, entitled“Pumping Cassette”; U.S. patent application Ser. No. 11/871,787, filedOct. 12, 2007, entitled “Pumping Cassette”; U.S. patent application Ser.No. 11/871,793, filed Oct. 12, 2007, entitled “Pumping Cassette”; U.S.patent application Ser. No. 11/871,803, filed Oct. 12, 2007, entitled“Cassette System Integrated Apparatus”; or in U.S. Pat. No. 8,042,563,issued Oct. 25, 2011, entitled “Cassette System Integrated Apparatus.”Each of these is incorporated by reference herein in their entireties.

A cassette may also include various features, such as pod pumps, fluidlines, valves, or the like. The cassette embodiments shown and describedin this description include exemplary and various alternate embodiments.However, any variety of cassettes is contemplated that include a similarfunctionality. Although the cassette embodiments described herein areimplementations of the fluid schematics as shown in the figures, inother embodiments, the cassette may have varying fluid paths and/orvalve placement and/or pod pump placements and numbers and thus, isstill within the scope of the invention.

In one example embodiment, a cassette may include a top plate, amidplate and a bottom plate. There are a variety of embodiments for eachplate. In general, the top plate includes pump chambers and fluid lines,the midplate includes complementary fluid lines, metering pumps andvalves and the bottom plate includes actuation chambers (and in someembodiments, the top plate and the bottom plate include complementaryportions of a balancing chamber or a pod pump).

In general, the diaphragms are located between the midplate and thebottom plate, however, with respect to a balancing chamber or a podpump, a portion of a diaphragm is located between the midplate and thetop plate. Some embodiments include where the diaphragm is attached tothe cassette, either overmolded, captured, bonded, press fit, welded inor any other process or method for attachment, however, in the exemplaryembodiments, the diaphragms are separate from the top plate, midplateand bottom plate until the plates are assembled.

The cassettes may be constructed of a variety of materials. Generally,in the various embodiment, the materials used are solid andnon-flexible. In one embodiment, the plates are constructed ofpolysulfone, but in other embodiments, the cassettes are constructed ofany other solid material and in exemplary embodiment, of anythermoplastic or thermoset.

In one exemplary embodiment, the cassettes are formed by placingdiaphragms in their correct locations (e.g., for one or more pod pumps,if such pod pumps are present), assembling the plates in order, andconnecting the plates. In one embodiment, the plates are connected usinga laser welding technique. However, in other embodiments, the plates maybe glued, mechanically fastened, strapped together, ultrasonicallywelded or any other mode of attaching the plates together.

In practice, the cassette may be used to pump any type of fluid from anysource to any location. The types of fluid include nutritive,nonnutritive, inorganic chemicals, organic chemicals, bodily fluids orany other type of fluid. Additionally, fluid in some embodiments includea gas, thus, in some embodiments, the cassette is used to pump a gas.

The cassette serves to pump and direct the fluid from and to the desiredlocations. In some embodiments, outside pumps pump the fluid into thecassette and the cassette pumps the fluid out. However, in someembodiments, the pod pumps serve to pull the fluid into the cassette andpump the fluid out of the cassette.

As discussed above, depending on the valve locations, control of thefluid paths is imparted. Thus, the valves being in different locationsor additional valves are alternate embodiments of this cassette.Additionally, the fluid lines and paths shown in the figures describedabove are mere examples of fluid lines and paths. Other embodiments mayhave more, less and/or different fluid paths. In still otherembodiments, valves are not present in the cassette.

The number of pod pumps (if pod pumps are present within the cassette)described above may also vary depending on the embodiment. For example,although the various embodiments shown and described above include twopod pumps, in other embodiments, the cassette includes one pod pump. Instill other embodiments, the cassette includes more than two pod pumps,or there may be no pod pumps present. The pod pumps may be single pumpsor multiple pod pumps may be present that can work in tandem, e.g., toprovide a more continuous flow, as discussed above. Either or both maybe used in various embodiments of the cassette. However, as noted above,in some cases, there may be pod pumps not present on a cassette, butcontained between two or more cassettes. Non-limiting examples of suchsystems can be seen in U.S. Pat. No. 8,042,563, issued Oct. 25, 2011,entitled “Cassette System Integrated Apparatus,” incorporated herein byreference.

The various fluid inlets and fluid outlets disclosed herein may be fluidports in some cases. In practice, depending on the valve arrangement andcontrol, a fluid inlet may be a fluid outlet. Thus, the designation ofthe fluid port as a fluid inlet or a fluid outlet is only fordescription purposes. The various embodiments have interchangeable fluidports. The fluid ports are provided to impart particular fluid pathsonto the cassette. These fluid ports are not necessarily all used all ofthe time; instead, the variety of fluid ports provides flexibility ofuse of the cassette in practice.

Another non-limiting example of a cassette is shown with reference toFIG. 46. Referring now to FIG. 46A, the assembled cassette systemintegrated is shown. The mixing cassette 500, middle cassette 600 andbalancing cassette 700 are linked by fluid lines or conduits. The podsare between the cassettes. Referring now to FIGS. 46B and 46C, thevarious views show the efficiency of the cassette system integrated. Thefluid lines or conduits 1200, 1300, 1400 are shown in FIG. 50A, FIG. 50Band FIG. 50C respectively. The fluid flows between the cassettes throughthese fluid lines or conduits. Referring now to FIGS. 50A and 50B, thesefluid lines or conduits represent larger 1300 and smaller 1200 checkvalve fluid lines. In the exemplary embodiment, the check valves areduck bill valves, however, in other embodiments, any check valve may beused. Referring to FIG. 50C, fluid line or conduit 1400 is a fluid lineor conduit that does not contain a check valve. For purposes of thisdescription, the terms “fluid line” and “conduit” are used with respectto 1200, 1300 and 1400 interchangeably.

Referring now to FIGS. 46B and 46C, and FIG. 51A, the following is adescription of one embodiment of the fluid flow through the variouscassettes. For ease of description, the fluid flow will begin with themixing cassette 500. Referring now to FIG. 46B and FIG. 51A, the fluidside of the mixing cassette 500 is shown. The fluid side includes aplurality of ports 8000, 8002, 8004, 8006, 8008 and 8010-8026 that areeither fluid inlets or fluid outlets. In the various embodiments, thefluid inlets and outlets may include one or more fluid inlets forreverse osmosis (“RO”) water 8004, bicarbonate, an acid, and a dialysate8006. Also, one or more fluid outlets, including a drain, acid 8002 andat least one air vent outlet as the vent for the dialysate tank. In oneembodiment, a tube (not shown) hangs off the outlet and is the vent (toprevent contamination). Additional outlets for water, bicarb and watermixture, dialysate mixture (bicarb with acid and water added) are alsoincluded.

The dialysate flows out of the mixing cassette 500, to a dialysate tank(not shown, shown as 1502 in FIG. 51A) and then through a conduit to theinner dialysate cassette 700 (pumped by the outer dialysate cassette 600pod pumps 602 and 604 (604 not shown, shown in FIGS. 46D and 46E). Thefluid paths within the cassettes may vary. Thus, the location of thevarious inlet and outlets may vary with various cassette fluid paths.

Referring now to FIG. 51B, in one embodiment of the cassette system, thecondo cells, conductivity and temperature sensors, are included in aseparate cassette 1504 outside of the cassette system shown in FIGS.46A-46C. This outside sensor cassette 1504 may be one of those describedin U.S. Pat. No. 8,491,184, issued Jul. 23, 2013, entitled “SensorApparatus Systems, Devices and Methods,” and hereby incorporated byreference in its entirety.

The fluid flow-path for this embodiment is shown in FIG. 51B. In thisembodiment, during the mixing process for the dialysate, the bicarbmixture leaves the mixing cassette 500 and flows to an outside sensorcassette, and then flows back into the mixing cassette 500. If thebicarb mixture meets pre-established thresholds, acid is then added tothe bicarb mixture. Next, once the bicarb and acid are mixed in themixing chamber 506, the dialysate flows out of the cassette into thesensor cassette and then back to the mixing cassette 500.

Referring now to FIG. 46D, the mixing cassette 500 include a pneumaticactuation side. In the block shown as 500, there are a plurality ofvalves and two pumping chambers 8030, 8032 build into the cassette 500for pumping or metering the acid or bicarb. In some embodiments,additional metering pumps, or less metering pumps, are included. Themetering pumps 8030, 8032 can be any size desired. In some embodiments,the pumps are different sizes with respect to one another, however, inother embodiments, the pumps are the same size with respect to oneanother. For example, in one embodiment, the acid pump is smaller thanthe bicarb pump. This may be more efficient and effective when using ahigher concentration acid, as it may be desirable to use a smaller pumpfor accuracy and also, it may be desirable for control schemes to have asmaller pump so as to use full strokes in the control rather thanpartial strokes.

The conduits 1200, 1300 include a check-valve. These conduits 1200,1300allow for one-way flow. In the exemplary embodiment, these conduits1200, 1300 all lead to drain. Referring to the flow-path schematic FIG.51A, the locations of these check-valve conduits are apparent. In theembodiment shown, any fluid that is meant for drain flows through themixing cassette 500. Referring again to FIG. 46B, a fluid drain port8006 is located on the fluid side of the cassette 500.

Once the dialysate is mixed, and after the dialysate flows to the sensorcassette (1504 in FIG. 51B) and it is determined that the dialysate isnot within set parameters/thresholds, then the dialysate will be pumpedback into the mixing cassette 500, through a plain conduit 1400 then tothe outer dialysate cassette 600, then back through conduit a checkvalve conduit 1200 and then through the mixing cassette 500 to the drainfluid outlet.

Referring now to FIGS. 46D and 46E, the various pods 502, 504, 506, 602,604, 702, 704, 706, 708 are shown. Each of the pod housings areconstructed identically, however, the inside of the pod housing isdifferent depending on whether the pod is a pod pump 502, 504, 602, 604,702, 704 a balancing chamber pods 706, 708 or a mixing chamber pod 504.

Referring now to FIGS. 46D and 46E, together with FIGS. 51A and 51B, thevarious pods are shown both in the fluid flow-path and on the cassettesystem. Pod 502 is the water pod pump and 504 is the bicarb water podpump (sends water to the bicarb) of the mixing cassette 500. Pod 506 isthe mixing chamber. Once the dialysate is mixed in the mixing chamber506, and then flows from the mixing cassette 500 to the sensor cassette1504, and it is determined that the dialysate qualifies as acceptable,then the dialysate flows to the dialysate tank 1502 through the mixingcassette dialysate tank outlet. However, if the dialysate is renderedunacceptable, then the fluid is pumped back into the cassette 500, thenthrough a 1400 conduit, to the outer dialysate cassette 600 and thenpumped through a 1200 check valve conduit, through the mixing cassette500 and out the drain outlet.

Referring to FIGS. 46A-46C, together with FIGS. 51A-B, the outerdialysate cassette is shown 600 between the mixing cassette 500 and theinner dialysate cassette 700. Pod pumps 602, 604, pump the dialysatefrom the dialysate tank 1502 and send it to the balancing chambers706,708 in the inner dialysate cassette 700 (driving force for thedialysate solution). The outer dialysate cassette 600 pushes thedialysate into the inner dialysate cassette (i.e., the pumps in theinner dialysate cassette 700 do not draw the dialysate in). Thus, fromthe outer dialysate cassette 600, the dialysate is pumped from thedialysate tank 1502, through a heater 1506 and through an ultrafilter1508, and then into the inner dialysate cassette 700.

Still referring now to FIGS. 46D and 46E, together with FIGS. 51A-B, theinner dialysate cassette 700 includes a metering pod 8038 (i.e., anultra filtration metering pod) and includes balancing pods 706, 708 andpod pumps 702, 704. The inner dialysate cassette 700 also includes fluidoutlets and inlets. These inlets and outlets include the outlet to thedialyzer 1510, the inlet from the dialyzer 1510, and a dialysate inlet(the ultrafilter 1508 connects to a port of the inner dialysatecassette). Fluid inlets and outlets are also included for the DCA andDCV connections during priming and disinfection. Various conduits(1200,1300,1400) serve as fluid connections between the cassettes 500,600, 700 and are used for dialysate fluid flow as well as fluid to passthrough in order to drain through the mixing cassette 500. The largestcheck valve 1300 (also shown in FIG. 50B) is the largest check-valve,and is used during disinfection. This tube is larger in order toaccommodate, in the preferred embodiment, blood clots and othercontaminants that flow through the conduits during disinfection.

The valves and pumps of the cassette system are pneumatically actuatedin the exemplary embodiment. The pneumatics attach to the cassettes viaindividual tubes. Thus, each pump, balancing pod, or valve includes anindividual tube connection to a pneumatic actuation manifold (notshown). Referring now to FIGS. 52A-F, the tubes are connected, in theexemplary embodiment, to at least one block, 1600. In some embodiments,more than one block is used to connect the various tubes. The block 1600is dropped into the manifold and then connected to the pneumaticsactuators appropriately. This allows for easy connection of thepneumatic tubes to the manifold.

Referring again to FIG. 46D, the cassette system includes springs 8034,in one embodiment, to aid in holding the system together. The springs8034 hook onto the mixing cassette 500 and inner dialysate cassette 700via catches 8036. However, in other embodiments, any other means orapparatus to assist in maintaining the system in appropriate orientationmay be used including, but not limited to, latching means or elasticmeans, for example.

Referring now to FIGS. 47A-47C, the exemplary embodiment of the pod isshown. The pod includes two fluid ports 902, 904 (an inlet and anoutlet) and the pod may be constructed differently in the variousembodiments. A variety of embodiments of construction are described inU.S. Pat. No. 8,292,594, issued Oct. 23, 2012 and entitled “FluidPumping Systems, Devices and Methods,” which is hereby incorporatedherein by reference in its entirety.

Referring now to FIGS. 47A, 47D and 47E the groove 906 in the chamber isshown. A groove 906 is included on each half of the pod housing. Inother embodiments, a groove is not included and in some embodiments, agroove is only included on one half of the pod.

Referring now to FIGS. 48A and 48B, the exemplary embodiment of themembrane used in the pod pumps 502, 504, 602, 604, 702, 704 is shown.This membrane is shown and described above with respect to FIG. 5A. Inother embodiments, any of the membranes shown in FIGS. 5B-5D may beused. An exploded view of a pod pump according to the exemplaryembodiment is shown FIG. 49.

Various aspects of the invention include one or more “pod pumps,” usedfor various purposes. The structure of a general pod pump will now bedescribed, although, as noted above, this structure may be modified forvarious uses, e.g., as a pump, a balancing chamber, a mixing chamber, orthe like. In addition, a pod pump may be positioned anywhere in thesystem, for instance, on a cassette or between two or more cassettes,etc.

Generally, a pod pump includes a rigid chamber (which may have anysuitable shape, e.g., spherical, ellipsoid, etc.), and the pod pump mayinclude a flexible diaphragm dividing each chamber into a first half anda second half. In some cases, the rigid chamber is a spheroid. As usedherein, “spheroid” means any three-dimensional shape that generallycorresponds to an oval rotated about one of its principal axes, major orminor, and includes three-dimensional egg shapes, oblate and prolatespheroids, spheres, and substantially equivalent shapes.

Each half of the pod pump may have at least one entry valve, and often(but not always) has at least one exit valve (in some cases, the sameport may be used for both entry and exit). The valves may be, forinstance, open/closing valves or two-way proportional valves. Forinstance, valves on one side of a chamber may be two-way proportionalvalves, one connected to a high pressure source, the other connected toa low pressure (or vacuum) sink, while the valves on the other half maybe opened and closed to direct fluid flow.

In some embodiments, the diaphragm has a variable cross-sectionalthickness. Thinner, thicker or variable thickness diaphragms may be usedto accommodate the strength, flexural and other properties of the chosendiaphragm materials. Thinner, thicker or variable diaphragm wallthickness may also be used to manage the diaphragm thereby encouragingit to flex more easily in some areas than in other areas, thereby aidingin the management of pumping action and flow of subject fluid in thepump chamber. In this embodiment, the diaphragm is shown having itsthickest cross-sectional area closest to its center. However in otherembodiments having a diaphragm with a varying cross-sectional, thethickest and thinnest areas may be in any location on the diaphragm.Thus, for example, the thinner cross-section may be located near thecenter and the thicker cross-sections located closer to the perimeter ofthe diaphragm. In one embodiment of the diaphragm, the diaphragm has atangential slope in at least one section, but in other embodiments, thediaphragm is completely smooth or substantially smooth.

The diaphragm may be made of any flexible material having a desireddurability and compatibility with the subject fluid. The diaphragm maybe made from any material that may flex in response to fluid, liquid orgas pressure or vacuum applied to the actuation chamber. The diaphragmmaterial may also be chosen for particular bio-compatibility,temperature compatibility or compatibility with various subject fluidsthat may be pumped by the diaphragm or introduced to the chambers tofacilitate movement of the diaphragm. In the exemplary embodiment, thediaphragm is made from high elongation silicone. However, in otherembodiments, the diaphragm is made from any elastomer or rubber,including, but not limited to, silicone, urethane, nitrile, EPDM or anyother rubber, elastomer or flexible material.

The shape of the diaphragm is dependent on multiple variables. Thesevariables include, but are not limited to: the shape of the chamber; thesize of the chamber; the subject fluid characteristics; the volume ofsubject fluid pumped per stroke; and the means or mode of attachment ofthe diaphragm to the housing. The size of the diaphragm is dependent onmultiple variables. These variables include, but are not limited to: theshape of the chamber; the size of the chamber; the subject fluidcharacteristics; the volume of subject fluid pumped per stroke; and themeans or mode of attachment of the diaphragm to the housing. Thus,depending on these or other variables, the shape and size of thediaphragm may vary in various embodiments.

The diaphragm may have any thickness. However, in some embodiments, therange of thickness is between 0.002 inches to 0.125 inches (1 inch=2.54cm). Depending on the material used for the diaphragm, the desiredthickness may vary. In one embodiment, high elongation silicone is usedin a thickness ranging from 0.015 inches to 0.050 inches. However inother embodiments, the thickness may vary.

In the exemplary embodiment, the diaphragm is pre-formed to include asubstantially dome-shape in at least part of the area of the diaphragm.Again, the dimensions of the dome may vary based on some or more of thevariables described above. However, in other embodiments, the diaphragmmay not include a pre-formed dome shape.

In the exemplary embodiment, the diaphragm dome is formed using liquidinjection molding. However, in other embodiments, the dome may be formedby using compression molding. In alternate embodiments, the diaphragm issubstantially flat. In other embodiments, the dome size, width or heightmay vary.

In various embodiments, the diaphragm may be held in place by variousmeans and methods. In one embodiment, the diaphragm is clamped betweenthe portions of the cassette, and in some of these embodiments, the rimof the cassette may include features to grab the diaphragm. In others ofthis embodiment, the diaphragm is clamped to the cassette using at leastone bolt or another device. In another embodiment, the diaphragm isover-molded with a piece of plastic and then the plastic is welded orotherwise attached to the cassette. In another embodiment, the diaphragmis pinched between a mid plate and a bottom plate. Although someembodiments for attachment of the diaphragm to the cassette aredescribed, any method or means for attaching the diaphragm to thecassette may be used. The diaphragm, in one alternate embodiment, isattached directly to one portion of the cassette. In some embodiments,the diaphragm is thicker at the edge, where the diaphragm is pinched bythe plates, than in other areas of the diaphragm. In some embodiments,this thicker area is a gasket, in some embodiments an O-ring, ring orany other shaped gasket.

In some embodiments of the gasket, the gasket is contiguous with thediaphragm. However, in other embodiments, the gasket is a separate partof the diaphragm. In some embodiments, the gasket is made from the samematerial as the diaphragm. However, in other embodiments, the gasket ismade of a material different from the diaphragm. In some embodiments,the gasket is formed by over-molding a ring around the diaphragm. Thegasket may be any shape ring or seal desired so as to complement the podpump housing embodiment. In some embodiments, the gasket is acompression type gasket.

Due to the rigid chamber, the pod pump has a generally constant volume.However, within the pod pump, the first and second compartments may havediffering volumes depending on the position of the flexible diaphragmdividing the chamber. Forcing fluid into one compartment may thus causethe fluid within the other compartment of the chamber to be expelled.However, the fluids are typically not able to come into direct contactwith each other within the pod pump due to the presence of the flexiblediaphragm.

Accordingly, in one embodiment, a pod pump used for pumping isconstructed to receive a control fluid in a first compartment and afluid to be pumped in a second compartment. The control fluid may be anyfluid, and may be a liquid or a gas. In one embodiment, the controlfluid is air. Drawing control fluid away from the pod pump (e.g.,through a vacuum, or at least a pressure lower than the pressure withinthe pod pump) causes the pod pump to draw in fluid (e.g., blood,dialysate, etc.) into the other compartment of the pod pump. Similarly,forcing control fluid into the pod pump (e.g., from a high pressuresource) causes the pod pump to expel fluid. By also controlling thevalves of the second compartment, fluid may be brought in through afirst valve and then expelled through a second valve due to action ofthe control fluid.

As another example, a pod pump may be used for fluid balancing, e.g., ofdialysate as discussed above. In such cases, instead of a control fluid,a fluid may be directed to each compartment of the pod pump. Asmentioned, the volume of the pod pump remains generally constant due tothe rigid chamber. Accordingly, when a first volume of fluid is drawninto a first compartment of a balancing pod, an equal volume of fluid isexpelled from the second compartment of the balancing pod (assuming thefluids to be generally incompressible under conditions in which the podis operated). Thus, using such balancing pods, equal volumes of fluidcan be moved. For instance, in FIG. 5, a balancing pod may allow freshdialysate to enter a first compartment and used dialysate to enter asecond compartment; the volumetric flows of fresh dialysate and useddialysate can be balanced against each other.

In some cases, a pod pump is used that does not contain a flexiblediaphragm dividing the chamber. In such instances, the pod pump can beused as a mixing chamber. For instance, mixing chamber 189 in FIG. 7Amay be such a pod pump.

A non-limiting example of a pod pump is shown in FIG. 9. This figure isa sectional view of a pneumatically controlled valve that may be used inembodiments of the cassettes. “Pneumatic,” as used herein, means usingair or other gas to move a flexible diaphragm or other member. (Itshould be noted that air is used by way of example only, and in otherembodiments, other control fluids, such as nitrogen (N₂), CO₂, water, anoil, etc. may be used). Three rigid pieces are used, a “top” plate 91, amiddle plate 92, and a “bottom” plate. (The terms “top” and “bottom”only refer to the orientation shown in FIG. 9. The valve may be orientedin any direction in actual use.) The top and bottom plates 91, 93 may beflat on both sides, while the middle plate 92 is provided with channels,indentations and holes to define the various fluid paths, chamber andports. A diaphragm 90, along with the middle plate 92, defines a valvingchamber 97. Pneumatic pressure is provided through a pneumatic port 96to either force, with positive gas pressure, the diaphragm 90 against avalve seat 99 to close the valve, or to draw, with negative gaspressure, the diaphragm away from the valve seat to open the valve. Acontrol gas chamber 98 is defined by the diaphragm 90, the top plate 91,and the middle plate 92. The middle plate 92 has an indentation formedon it, into which the diaphragm 90 is placed so as to form the controlgas chamber 98 on one side of the diaphragm and the valving chamber 97on the other side.

The pneumatic port 96 is defined by a channel formed on the “top”surface of the middle plate 92, along with the top plate 91. Byproviding fluid communication between several valving chambers in acassette, valves may be ganged together so that all the valves gangedtogether may be opened or closed at the same time by a single source ofpneumatic pressure. Channels formed on the “bottom” surface of themiddle plate 92, along with the bottom plate, define the valve inlet 94and the valve outlet 95. Holes formed through the middle plate 92provide communication between the inlet 94 and the valving chamber 97(through the valve seat 99) and between the valving chamber and theoutlet 95.

The diaphragm 90 is provided with a thickened rim 88, which fits tightlyin a groove 89 in the middle plate 92. Thus, the diaphragm 90 may beplaced in and held by the groove 88 before the top plate 91 isultrasonically welded to the middle plate 92, so the diaphragm will notinterfere with the ultrasonic welding of the two plates together, and sothat the diaphragm does not depend on the two plates beingultrasonically welded together in just the right way to be held inplace. Thus, this valve may be manufactured easily without relying onultrasonic welding to be done to very tight tolerances. As shown in FIG.9, the top plate 91 may include additional material extending intocontrol gas chamber 98 so as to prevent the diaphragm 90 from beingurged too much in a direction away from the groove 89, so as to preventthe diaphragm's thickened rim 88 from popping out of the groove 89.

Pressure sensors may be used to monitor pressure in the pods. Forinstance by alternating applied air pressure to the pneumatic side ofthe chamber, the diaphragm is cycled back and forth across the totalchamber volume. With each cycle, fluid is drawn through the upstreamvalve of the inlet fluid port when the pneumatics pull a vacuum on thepods. The fluid is then subsequently expelled through the outlet portand the downstream valve when the pneumatics deliver positive pressureto the pods.

FIG. 10 is a sectional view of one embodiment of a pod pump that may beincorporated into embodiments of the fluid-control cassettes. In someembodiments, the cassette would incorporate several pod pumps andseveral valves made in accordance with the construction techniques shownin FIGS. 9 and 10. In such embodiments, the pod pump of FIG. 10 is madefrom different portions of the same three rigid pieces used to make thevalve of FIG. 9. These rigid pieces are the “top” plate 91, the middleplate 92, and the “bottom” plate. (As noted above, the terms “top” and“bottom” only refer to the orientation shown in FIG. 9.) To form the podpump, the top and bottom plates 91, 93 may include generallyhemispheroid portions that together define a hemispheroid pod pump.

A diaphragm 109 separates the central cavity of the pod pump into achamber (the pumping chamber) that receives the fluid to be pumped andanother chamber (the actuation chamber) for receiving the control gasthat pneumatically actuates the pump. An inlet 94 allows fluid to enterthe pumping chamber, and an outlet allows fluid to exit the pumpingchamber. The inlet 94 and the outlet 95 may be formed between middleplate 92 and the bottom plate 93. Pneumatic pressure is provided througha pneumatic port 106 to either force, with positive gas pressure, thediaphragm 109 against one wall of pod pump's cavity to minimize thepumping chamber's volume (as shown in FIG. 10), or to draw, withnegative gas pressure, the diaphragm towards the other wall of the podpump's cavity to maximize the pumping chamber's volume.

In some embodiments of the pod pump, various configurations, includinggrooving on one or more plates exposed to the cavity of the pod pump,are used. Amongst other benefits, grooving can prevent the diaphragmfrom blocking the inlet or outlet (or both) flow path for fluid or air(or both).

The diaphragm 109 may be provided with a thickened rim 88, which is heldtightly in a groove 89 in the middle plate 92. Thus, like in the valvingchamber of FIG. 9, the diaphragm 109 may be placed in and held by thegroove 89 before the top plate 91 is ultrasonically welded to the middleplate 92, so the diaphragm will not interfere with the ultrasonicwelding of the two plates together, and so that the diaphragm does notdepend on the two plates being ultrasonically welded together in justthe right way to be held in place. Thus, this pod pump can bemanufactured easily without relying on ultrasonic welding to be done tovery tight tolerances.

FIG. 11A is a schematic view showing an embodiment of a pressureactuation system 110 for a pod pump, such as that shown in FIG. 10. Inthis example, air is used as a control fluid (e.g., such that the pumpis pneumatically driven). As mentioned, other fluids (e.g., water) mayalso be used as control fluids in other embodiments.

In FIG. 11A, pressure actuation system 110 alternately provides positiveand negative pressurizations to the gas in the actuation chamber 112 ofthe pod pump 101. The pneumatic actuation system 110 includes anactuation-chamber pressure transducer 114, a variable positive-supplyvalve 117, a variable negative-supply valve 118, a positive-pressure gasreservoir 121, a negative-pressure gas reservoir 122, apositive-pressure-reservoir pressure transducer 115, anegative-pressure-reservoir pressure transducer 116, as well as anelectronic controller 119.

The positive-pressure reservoir 121 provides to the actuation chamber112 the positive pressurization of a control gas to urge the diaphragm109 towards a position where the pumping chamber 111 is at its minimumvolume (i.e., the position where the diaphragm is against the rigidpumping-chamber wall). The negative-pressure reservoir 122 provides tothe actuation chamber 112 the negative pressurization of the control gasto urge the diaphragm 109 in the opposite direction, towards a positionwhere the pumping chamber 111 is at its maximum volume (i.e., theposition where the diaphragm is against the rigid actuation-chamberwall).

A valving mechanism is used in this example to control fluidcommunication between each of these reservoirs 121, 122 and theactuation chamber 112. In FIG. 11A, a separate valve is used for each ofthe reservoirs; a positive-supply valve 117 controls fluid communicationbetween the positive-pressure reservoir 121 and the actuation chamber112, and a negative-supply valve 118 controls fluid communicationbetween the negative-pressure reservoir 122 and the actuation chamber112. These two valves are controlled by an electronic controller 119.(Alternatively, a single three-way valve may be used in lieu of the twoseparate valves 117, 118.) In some cases, the positive-supply valve 117and the negative-supply valve 118 are variable-restriction valves, asopposed to binary on-off valves. An advantage of using variable valvesis discussed below.

The controller 119 also receives pressure information from the threepressure transducers shown in FIG. 11A: an actuation-chamber pressuretransducer 114, a positive-pressure-reservoir pressure transducer 115,and a negative-pressure-reservoir pressure transducer 116. As theirnames suggest, these transducers respectively measure the pressure inthe actuation chamber 112, the positive-pressure reservoir 121, and thenegative-pressure reservoir 122. The controller 119 monitors thepressure in the two reservoirs 121, 122 to ensure they are properlypressurized (either positively or negatively). A compressor-type pump orpumps may be used to attain the desired pressures in these reservoirs121, 122.

In one embodiment, the pressure provided by the positive-pressurereservoir 121 is strong enough, under normal conditions, to urge thediaphragm 109 all the way against the rigid pumping-chamber wall.Similarly, the negative pressure (i.e., the vacuum) provided by thenegative-pressure reservoir 122 is preferably strong enough, undernormal conditions, to urge the diaphragm all the way against the rigidactuation-chamber wall. In some embodiments, however, these positive andnegative pressures provided by the reservoirs 121, 122 are within safeenough limits that even with either the positive-supply valve 117 or thenegative-supply valve 118 open all the way the positive or negativepressure applied against the diaphragm 109 is not so strong as to harmthe patient.

In one embodiment, the controller 119 monitors the pressure informationfrom the actuation-chamber-pressure transducer 114 and, based on thisinformation, controls the valving mechanism (valves 117, 118) to urgethe diaphragm 109 all the way to its minimum-pumping-chamber-volumeposition and then after this position is reached to pull the diaphragm109 all the way back to its maximum-pumping-chamber-volume position.

The pressure actuation system (including the actuation-chamber pressuretransducer 114, the positive-pressure-reservoir pressure transducer 115,the negative-pressure-reservoir pressure transducer 116, the variablepositive-supply valve 117, the variable negative-supply valve 118, thecontroller 119, the positive-pressure gas reservoir 121, and thenegative-pressure gas reservoir 122) is located entirely or mostlyoutside the insulated volume (item 61 of FIG. 6). The components thatcome into contact with blood or dialysate (namely, pod pump 101, theinlet valve 105 and the outlet valve 107) may be located, in some cases,in the insulated volume so that they can be more easily disinfected.

Another example of a pressure actuation system 110 for a pod pump isillustrated in FIG. 11B. In this example, pod pump 101 includes apumping chamber 111, an actuation chamber 112, and a diaphragm 109separating the two sides. Fluid ports 102 and 104 allow access of fluidin and out of pumping chamber 111, e.g., through the use of fluid valves(not shown). Within pod pump 101, however, fluid ports 102 and 104include a “volcano” port 126, generally having a raised shape, such thatwhen diaphragm 109 contacts the port, the diaphragm is able to form atight seal against the port. Also shown in FIG. 11B is a 3-way valveconnecting pressure reservoirs 121, 122. The 3-way valve 123 is in fluidcommunication with actuation chamber 112 by a single port in thisexample.

It will be appreciated that other types of actuation systems may be usedto move the diaphragm back and forth instead of the two-reservoirpneumatic actuation system shown in FIGS. 11A-11B.

As noted above, the positive-supply valve 117 and the negative-supplyvalve 118 in the pneumatic actuation system 110 of FIG. 11A arepreferably variable-restriction valves, as opposed to binary on-offvalves. By using variable valves, the pressure applied to the actuationchamber 112 and the diaphragm 109 can be more easily controlled to bejust a fraction of the pressure in reservoir 121, 122, instead ofapplying the full reservoir pressure to the diaphragm. Thus, the samereservoir or set of reservoirs may be used for different pod pumps, eventhough the pressures for operating the pod pumps may differ from podpump to pod pump. Of course, the reservoir pressure needs to be greaterthan the desired pressures to be applied to various pod pump'sdiaphragms, but one pod pump may be operated at, say, half of thereservoir pressure, and another pod pump may be actuated with the samereservoir but at, say, a quarter of the reservoir pressure. Thus, eventhough different pod pumps in the dialysis system are designed tooperate at different pressures, these pod pumps may all share the samereservoir or set of reservoirs but still be actuated at differentpressures, through the use of variable valves. The pressures used in apod pump may be changed to address conditions that may arise or changeduring a dialysis procedure. For example, if flow through the system'stubing becomes constricted because the tubes get twisted, one or both ofthe positive or negative pressures used in the pod pump may be increasedin order to over compensate for the increased restriction.

FIG. 12 is a graph showing how pressures applied to a pod pump may becontrolled using variable valves. The vertical axis represents pressurewith P_(R+) and P_(R−) representing respectively the pressures in thepositive and negative reservoirs (items 121 and 122 in FIG. 11A), andP_(C+) and P_(C−) representing respectively the positive and negativecontrol pressures acting on the pod pump's diaphragm. As can be seen inFIG. 12, from time T₀ to about time T₁, a positive pressure is appliedto the actuation chamber (so as to force fluid out of the pumpingchamber). By repeatedly reducing and increasing the flow restrictioncaused by the positive variable valve (item 117 in FIG. 11A), thepressure being applied to the actuation chamber can be held at about thedesired positive control pressure, P_(C+). The pressure varies, in asinusoidal manner, around the desired control pressure. Anactuation-chamber pressure transducer (item 114 in FIG. 11A) incommunication with the actuation chamber measures the pressure in theactuation chamber and passes the pressure-measurement information to thecontroller (item 119 in FIG. 11A), which in turn controls the variablevalve so as to cause the actuation chamber's pressure to vary around thedesired control pressure, P_(C+). If there are no fault conditions, thediaphragm is pushed against a rigid wall of the pumping chamber, therebyending the stroke. The controller determines that the end of stroke hasbeen reached when the pressure measured in the actuation chamber nolonger drops off even though the restriction created by the variablevalve is reduced. In FIG. 12, the end of the expelling stroke occursaround time T₁. When the end of stroke is sensed, the controller causesthe variable valve to close completely so that the actuation chamber'spressure does not increase much beyond the desired control pressure,P_(C+).

After the positive variable valve is closed, the negative variable valve(item 118 in FIG. 11A) is partially opened to allow the negativepressure reservoir to draw gas from the actuation chamber, and thus drawfluid into the pumping chamber. As can be seen in FIG. 12, from a timeshortly after T₁ to about time T₂, a negative pressure is applied to theactuation chamber). As with the expelling (positive pressure), strokedescribed above, repeatedly reducing and increasing the flow restrictioncaused by the negative variable valve can cause the pressure beingapplied to the actuation chamber can be held at about the desirednegative control pressure, P_(C−) (which is weaker than the pressure inthe negative pressure reservoir). The pressure varies, in a sinusoidalmanner, around the desired control pressure. The actuation-chamberpressure transducer passes pressure-measurement information to thecontroller, which in turn controls the variable valve so as to cause theactuation chamber's pressure to vary around the desired controlpressure, P_(C−). If there are no fault conditions, the diaphragm ispulled against a rigid wall of the actuation chamber, thereby ending thedraw (negative pressure) stroke. As described above, the controllerdetermines that the end of stroke has been reached when the partialvacuum measured in the actuation chamber no longer drops off even thoughthe restriction created by the variable valve is reduced. In FIG. 12,the end of the draw stroke occurs around time T₂. When the end of strokeis sensed, the controller causes the variable valve to close completelyso that the actuation chamber's vacuum does not increase much beyond thedesired negative control pressure, P_(C−). Once the draw stroke hasended, the positive variable valve can be partially opened to begin anew expelling stroke with positive pressure.

Thus, each pod pump in this example uses the two variable-orifice valvesto throttle the flow from the positive-pressure source and into thenegative-pressure. The pressure in the actuation chamber is monitoredand a controller uses this pressure measurement to determine theappropriate commands to both valves to achieve the desired pressure inthe actuation chamber. Some advantages of this arrangement are that thefilling and delivering pressure may be precisely controlled to achievethe desired flow rate while respecting pressure limits, and that thepressure may be varied with a small sinusoidal signature command. Thissignature may be monitored to determine when the pump reaches the end ofa stroke.

Another advantage of using variable valves in this way, instead ofbinary valves, is that by only partially opening and closing thevariable valves the valves are subject to less wear and tear. Therepeated “banging” of binary valves all the way opened and all the wayclosed can reduce the life of the valve.

If the end of stroke is detected and the integrated value of thecorrelation function is very small, this may be an indication that thestroke occluded and did not complete properly. It may be possible todistinguish upstream occlusions from downstream occlusions by looking atwhether the occlusion occurred on a fill or a delivery stroke (this maybe difficult for occlusions that occur close to the end of a stroke whenthe diaphragm is near the chamber wall). FIGS. 13A-13B depict occlusiondetection (the chamber pressure drops to 0 when an occlusion isdetected).

Under normal operation, the integrated value of the correlation functionincreases as the stroke progresses. If this value remains small or doesnot increase the stroke is either very short (as in the case of a verylow impedance flow or an occlusion) or the actual pressure may not betracking the desired sinusoidal pressure due to a bad valve or pressuresignals. Lack of correlation can be detected and used for error handlingin these cases.

Under normal circumstances when the flow controller is running, thecontrol loop will adjust the pressure for any changes in flow rate. Ifthe impedance in the circuit increases dramatically and the pressurelimits are saturated before the flow has a chance to reach the targetrate, the flow controller will not be capable of adjusting the pressureshigher to reach the desired flow rate. These situations may arise if aline is partially occluded, such as when a blood clot has formed in thecircuit. Pressure saturation when the flow has not reached the targetflow rate can be detected and used in error handling.

If there are problems with the valves or the pneumatics such as aleaking fluid valve or a noisy pressure signal, ripple may continue onthe stroke indefinitely and the end of stroke algorithm may not seeenough of a change in the pressure ripple to detect end of stroke. Forthis reason a safety check is added to detect if the time to complete astroke is excessive. This information can be used for error handling.

In a dual pump, such as pump 13 in FIG. 3A, the two pump chambers may becycled in opposite directions to affect the pumping cycle. A phaserelationship from 0° (both chambers act in the same direction) to 180°(chambers act in opposite directions) can be selected. Phase movementmay be modified somewhat in certain cases because it may not be possibleto move both chambers in the same direction simultaneously; doing socould have both input or output valves open and end of stroke will notbe detected properly.

Selecting a phase relationship of 180° yields continuous flow into andout of the pod. This is the nominal pumping mode when continuous flow isdesired. Setting a phase relationship of 0° is useful for single needleflow. The pods will first fill from the needle and then deliver to thesame needle. Running at phases between 0 and 180 degrees can be used toachieve a push/pull relationship (hemodiafiltration/continuous backflush) across the dialyzer. FIGS. 8A-8C are graphical representations ofsuch phase relationships.

The pod pumps may control flow of fluid through the various subsystems.For instance, a sinusoidal pressure waveform may be added to a DCpressure command to make up the commanded pressure signal for the podpumps. When the diaphragm is moving, the pressure in the pods tracks thesinusoidal command. When the diaphragm comes in contact with the chamberwall and is no longer moving, the pressure in the pod remains constantand does not track the sinusoidal input command. This difference in thepressure signal command following of the pods is used to detect the endof a stroke. From the end of stroke information, the time for eachstroke is calculated. Knowing the volume of the pods and the time tocomplete a stroke, a flow rate for each pod can be determined. The flowrate is fed back in a PI loop in order to calculate the required DCpressure for the next stroke.

The amplitude of the sinusoidal input may be selected such it is largeenough for the actual pressure to reasonably track the command and smallenough such that when it is subtracted from the minimum DC pump pressureand applied to the pod, the pressure is sufficient to cause thediaphragm to move under expected operating conditions of fluidviscosity, head height and fluid circuit resistance. The frequency ofthe sinusoidal input was selected empirically such that it is possibleto reliably detect end of stroke. The more cycles of the sine wave perstroke, the more accurate the end of stroke detection algorithm.

To detect the change in the command following of the pod pressure, thepressure signal in the pods is sent through a cross correlation filter.The size of the sampling window for the cross correlation filter isequivalent to the period of the input sine wave. For every sample in thewindow the commanded pressure signal is multiplied by the previoussample of the actual pressure and added to the previous correlationvalue. The window is then shifted by one frame and the process isrepeated. The resulting product is then differentiated and passedthrough a second order filter with a corner frequency the same as theinput sine wave frequency and a damping ratio of one. The effect of thisfilter is to act as a band pass filter, isolating correlated signals atthe input sinusoidal frequency. The absolute value of the output of thisfilter is then passed through a second order low pass filter with thesame frequency of the sinusoidal frequency and a damping ratio of 3.0.This second filter is used integrate the differentiated signal to and toreduce noise in the resulting signal. If the two signals are correlated,the resulting filtered value will be large. If the two signals are notcorrelated (for example at end of stroke), the resulting filtered valuewill be small. The end of stroke can be detected when the filtered crosscorrelation signal drops below a particular threshold, or when thesignal drops off a by a percentage of its maximum value through out thestroke. To tune performance for a particular pumping scenario, thisthreshold or percent drop can be varied as a function of pressure orflow rate.

Since the end of stroke algorithm typically takes about one cycle of thesinusoidal ripple to detect end of stroke, minimizing this cycle time(maximizing the sine wave frequency) reduces the delay at the end ofstroke. Low pressure, high frequency flows are not well tracked by thecontroller. Lower pressure strokes tend to have lower flow rates andthus the delay at the end of stroke is a lesser percentage of the totalstroke time. For this reason, the frequency can be lower for lowpressure strokes. Frequency of the sine wave can be adjusted as a linearfunction of the delivery pressures. This insures minimum delays when thestrokes are the shortest. When the frequency of the sine wave for thedesired pressure is changed, the filters for the cross correlationfunction must also be adjusted. Filters are set up to continuouslycalculate the filter coefficients based on this changing frequency.

Pressure in the pod chambers may also be controlled using two variablesolenoid valves; one connecting the plenum to a higher pressure source,the second connecting the plenum to lower pressure (or vacuum) sink.Solenoid valves tend to have a large dead band region so a non-linearoffset term is added to the controller to compensate.

A diagram of an example control algorithm is shown in FIG. 14. Thecontroller in this example is a standard discrete PI controller. Theoutput of the PI controller is split into two paths; one for the sourcevalve, one to the sink valve. An offset term is added to each of thesepaths to compensate for the valve dead band. The resulting command isthen limited to valves greater than zero (after being inverted in thecase of the sink valve).

The offset term is positive in the case of the source valve, andnegative in the case of the sink valve. As a result, both valves will beactive even as the error goes to zero. These offsets do improve thetrajectory following and disturbance rejection ability of thecontroller, but can also result in leakage from both valves at steadystate if the command offsets are slightly larger than the actual valvedead band. If this is the case, the valves will have equal and oppositeleakage mass flows at steady state.

To eliminate this leakage mass flow when the control system is idle, a“power save” block can be added to turn off the valves if the absolutevalue of the error term remains small for a period of time. This isanalogous to using mechanical brakes on a servomotor.

Referring now to FIG. 15, the controller in this example uses a standarddiscrete PI regulator; a diagram of the PI regulator is shown. Theintegrator can be limited to prevent wind up when the commands aresaturated. The integrator will always be capable of unwinding. Becausethere are different amounts of air in the pod for a fill and a deliverstroke, the response of the pod can be very different for a fill anddeliver stroke. The proportional gain is adjusted differently for a filland deliver stroke to better tune for the different pod responses.

The saturation limits chosen for the PI regulator should take intoaccount the offset that will be added to the result. For example, if thevalve saturates at 12V and a 5V fixed offset will be added after the PIloop, the saturation limit in the PI loop should be set to 7V. Thispositive and negative saturation limits will likely be different due tothe different dead band in the source and sink valves.

During a fill stroke, the upstream fluid valve is closed and the downstream fluid valve is opened to allow fluid flow into the chamber.During a delivery stroke the upstream fluid valve is opened and thedownstream fluid valve is closed to allow fluid flow out of the chamber.At the end of stroke, and until the next stroke starts, both fluidvalves are closed.

As discussed, in certain aspects, a pod pump may be operated throughaction of a control fluid, for example, air, nitrogen, water, an oil,etc. The control fluid may be chosen to be relatively incompressible,and in some cases, chosen to be relatively inexpensive and/or non-toxic.The control fluid may be directed into the system towards the pumpsusing a series of tubes or other suitable conduits. A controller maycontrol flow of control fluid through each of the tubes or conduits. Insome cases, the control fluid may be held at different pressures withinthe various tubes or conduits. For instance, some of the control fluidmay be held at positive pressure (i.e., greater than atmosphericpressure), while some of the control fluid may be held at negativepressures (less than atmospheric pressure) or even zero pressure (i.e.,vacuum). As a specific, non-limiting example, a pod pump such as the oneillustrated in FIG. 11A may be controlled through operation of thecontrol fluid by the controller. As previously discussed, the controller(119) may open and close valves (e.g., valves 117 and 118) to expose thepneumatic side of the pod pump to a positive pressure (121) or a vacuumpressure (122) at different points during a pumping cycle.

In addition, in certain embodiments, the controller (typicallyelectronic) may also be kept separate from the various fluid circuits,such that there is no electronic contact between the controller and thevarious fluid circuits, although the control fluid (e.g., air) is ableto pass between the controller and the various pumps. This configurationhas a number of advantages, including ease of maintenance (thecontroller and the various circuits can be repaired independently ofeach other). In one embodiment, the fluid circuits may be heated todisinfection temperatures and/or exposed to relatively high temperaturesor other harsh conditions (e.g., radiation) to effect disinfection,while the electronic controller (which is typically more delicate) isnot exposed to such harsh conditions, and may even be kept separate byan insulating wall (e.g., a “firewall”) or the like.

Thus, in some embodiments, the system may include a “cold” section(which is not heated), and a “hot” section, portions of which may beheated, e.g., for disinfection purposes. The cold section may insulatedfrom the hot section through insulation. In one embodiment, theinsulation may be molded foam insulation, but in other embodiments canbe any type of insulation, including but not limited to a sprayinsulation or an insulation cut from sheets.

In some cases, the “hot” section may be heated to relatively hightemperatures, e.g., the “hot” section may be heated to temperaturessufficient to sterilize components within the “hot” section. As manyelectronics can not go above 50° C. without failing or other adverseconsequences, it may be advantageous in some embodiments to separate theelectronics from other components that may be disinfected. Thus, in somecases, the components that may need to be disinfected are kept in the“hot” section, while components that cannot be heated to suchtemperatures are kept in the “cold” section. In one embodiment, the coldsection includes a circulation system, e.g., a fan and/or a grid toallow air to flow in and out of the cold box.

All, or a portion of, the “hot” section may be encased in insulation. Insome cases, the insulation may be extended to cover access points to the“hot” section, e.g., doors, ports, gaskets, and the like. For instance,when the “hot” section is sealed, the insulation may completely surroundthe “hot” section in some cases.

Non-limiting examples of components that may be present within the“cold” section include power supplies, electronics, power cables,pneumatic controls, or the like. In some cases, at least some of thefluids going to and from the “hot” section may pass through the “cold”section; however, in other cases, the fluids may pass to the “hot”section without passing through the “cold” section.

Non-limiting examples of components that may be present within the “hot”section include cassettes (if present), fluid lines, or the like. Insome cases, some electrical components may also be included in the “hot”section. These include, but are not limited to, a heater. In oneembodiment, the heater can be used to heat the hot box itself, inaddition to fluid (see, e.g., heater 72 of FIG. 3A). In someembodiments, the heater heats the entire “hot” section to reach adesired temperature.

In one embodiment, the “hot” section includes some or all of the fluidiclines. In addition, in some cases, the “hot” section may include, but isnot limited to, temperature and conductivity sensors, blood leaksensors, heaters, other sensors, switches, emergency lights, or thelike.

In some cases, a manifold may transition from the “cold” section to the“hot” section, e.g., a manifold for air or another control fluid.

Separating the components into “hot” and “cold” sections may offerseveral advantages; those include, but are not limited to: longevity ofelectrical components, reliability, or efficiency. For example, byseparating the components into hot and cold, the entire hot box may beheated. This may allow for more efficient use of heat which leads to amore energy efficient system. This also may allow for the use ofstandard, off the shelf electronics which leads to lower cost.

In some embodiments, the control fluid used for controlling the pumps,valves, etc. is air, and the air may be brought into the system throughthe operation of one or more air compressors. In some cases, the aircompressor may be kept separate from the blood flow path and thedialysate flow path systems within the system, and air from the aircompressor may be brought to the various pumps through various tubes,conduits, pipes, or the like. For example, in one embodiment, apneumatic interface is used to direct air from the air compressor to aseries of tubes or conduits fluidically connected with the various pumpsor chambers.

A non-limiting example can be seen in FIG. 16, which shows a schematicrepresentation of a dual-housing arrangement according to oneembodiment. This arrangement may be advantageously used with cassettesthat include many pneumatically actuated pumps and/or valves. If thenumber of pneumatically actuated pumps and/or valves in a cassette islarge enough, the cassette containing these pumps and valves can becomeso large, and the pressures involved can become so great, that it maybecome difficult to properly seal and position all of the pumps andvalves. This difficulty may be alleviated by using two or more differenthousings. The valves and pumps (such as pod pumps 42) are placed in amain housing 41, from which connecting tubes 45 lead from pneumaticports 44. The main housing 41 also has inlet and outlet tubes 43, whichallow liquid to flow into and out of the main housing. The connectingtubes 45 provide pneumatic communication between valves and pumps in themain housing 41 and a smaller, secondary tube-support housing 46, whichis provided with a pneumatic interface 47 for each of the tubes. Theproper positioning and sealing of all the pneumatic interfaces 47against receptacles in the base unit can be accomplished more easilywith the smaller tube-support housing 46 than it would be if thepneumatic actuation was applied to the larger main housing directly.

The control fluid (e.g., air) may be supplied to the system with one ormore supply tanks or other pressure sources, in one set of embodiments.For instance, if two tanks are used, one supply tank may be a positivepressure reservoir, and in one embodiment, has a set point of 750 mmHg(gauge pressure) (1 mmHg is about 133.3 pascals). The other supply tankcan be a vacuum or negative pressure reservoir, and in one embodiment,has a set point of −450 mmHg (gauge pressure). This pressure differencemay be used, for instance, between the supply tanks and the required podpressure to allow for accurate control of the variable valves to the podpumps. The supply pressure limits can be set based on maximum pressuresthat can be set for the patient blood flow pump plus some margin toprovide enough of a pressure difference for control of the variablevalves. Thus, in some cases, the two tanks may be used to supplypressures and control fluids for the entire system.

In one embodiment, two independent compressors service the supply tanks.Pressure in the tanks can be controlled using any suitable technique,for instance, with a simple bang-bang controller (a controller thatexists in two states, i.e., in an on or open state, and an off or closedstate), or with more sophisticated control mechanisms, depending on theembodiment. As an example of a bang-bang controller, for the positivetank, if the actual pressure is less than the desired pressure minus ahysteresis, the compressor servicing the positive tank is turned on. Ifthe actual pressure is greater than the desired pressure plus ahysteresis, the compressor servicing the positive tank is turned off.The same logic may be applied to the vacuum tank and control of thevacuum compressor with the exception that the sign of the hysteresisterm is reversed. If the pressure tanks are not being regulated, thecompressor is turned off and the valves are closed.

Tighter control of the pressure tanks can be achieved by reducing thesize of the hysteresis band, however this will result in higher cyclingfrequencies of the compressor. If very tight control of these reservoirsis required, the bang-bang controller could be replaced with a PIDcontroller and using PWM signals on the compressors. Other methods ofcontrol are also possible.

However, other pressure sources may be used in other embodiments, and insome cases, more than one positive pressure source and/or more than onenegative pressure source may be used. For instance, more than onepositive pressure source may be used that provides different positivepressures (e.g., 1000 mmHg and 700 mmHg), which may be used to minimizeleakage. A non-limiting example of a negative pressure is −400 mmHg. Insome cases, the negative pressure source may be a vacuum pump, while thepositive pressure pump may be an air compressor.

Certain aspects of the invention include various sensors; for instance,in various embodiments of the inventions described herein, systems andmethods for fluid handling may be utilized that comprise sensorapparatus systems comprising a sensor manifold. Examples of suchembodiments may include systems and methods for the diagnosis,treatment, or amelioration of various medical conditions, includingembodiments of systems and methods involving the pumping, metering,measuring, controlling, and/or analysis of various biological fluidsand/or therapeutic agents, such as various forms of dialysis, cardiacbypass, and other types of extracorporeal treatments and therapies.Further examples include fluid treatment and preparation systems,including water treatment systems, water distillation systems, andsystems for the preparation of fluids, including fluids utilizeddiagnosis, treatment, or amelioration of various medical conditions,such as dialysate.

Examples of embodiments of the inventions described herein may includedialysis systems and methods. More specifically, examples of embodimentsof the inventions described herein may include hemodialysis systems andmethods of the types described in U.S. Pat. No. 8,273,680, issued Sep.25, 2012, entitled “Pumping Cassette”; or U.S. Pat. No. 8,042,563,issued Oct. 25, 2011, entitled “Cassette System Integrated Apparatus.”each of which are incorporated herein by reference.

In such systems and methods, the utilization of one or more sensormanifolds may allow subject media to be moved from one environment toanother environment that is more conducive to obtaining sensor readings.For example, the cassette manifold may be contained in an area that isless subject to various types of environment conditions, such astemperature and/or humidity, which would not be preferable for sensorapparatus such as a sensing probe. Alternatively, sensing apparatus andsensing apparatus system may be delicate and may be more prone tomalfunctions than other components of a system. Separating the sensorapparatus and the sensor apparatus systems from other components of thesystem by use of a sensor manifold may allow the sensing apparatus andsensing apparatus systems to be checked, calibrated, repaired orreplaced with minimal impact to other components in the system. Theability to check, calibrate, repair or replace the sensor manifold withminimal impact to the remainder of the system may be advantageous whenutilized in connection with the integrated cassette systems and methodsdescribed in U.S. Pat. No. 8,042,563, issued Oct. 25, 2011, entitled“Cassette System Integrated Apparatus.” Alternatively, the sensormanifold may be replaced either more or less frequently than othercomponents of the system.

With reference to FIGS. 53-58, various embodiments of an exemplarysensor manifold are shown. One or more subject media, e.g., a liquid inthese exemplary embodiments, may be contained in or flow throughcassette manifold 4100. For example, one subject media may entercassette manifold 4100 via pre-molded tube connector 4101 and exit thecassette manifold via pre-molded tube connector 4102. Between tubeconnector 4101 and 4102, there is a fluid path though the cassette (bestshown as fluid path 4225 in FIG. 54) Likewise, fluid paths (shown asfluid paths 4223, 4220, 4222, 4224, and 4221 respectively in FIG. 54)extend between sets of tube connectors 4103 and 4104; 4105 and 4106;4107, 4108, and 4109; 4110 and 4111; and 4112 and 4113. In certainembodiments, each fluid path may contain subject media of differentcomposition or characteristics. In other embodiments, one or more fluidpaths may contain the same or similar subject media. In certainembodiments, the same subject media may be flowed through more than oneflow path at the same time to check and/or calibrate the sensorapparatus systems associated with such fluid paths.

Referring now to FIG. 55, in these exemplary embodiments of sensormanifold 4100 that may be used in conjunction with the sensor apparatusand sensor apparatus systems described herein, the cassette includes atop plate 4302 and a base 4301. Fluid paths, such as the fluid path 4225(as shown in FIG. 54) extending between tube connectors 4101 and 4102extend between the base and top plate. The cassettes may be constructedfrom a variety of materials. Generally, in the various exemplaryembodiment, the materials used are solid and non flexible. In thepreferred embodiment, the plates are constructed of polysulfone, but inother embodiments, the cassettes are constructed of any other solidmaterial and in exemplary embodiments, of any thermoplastic. Someembodiments of sensor manifold 4100 may be fabricated utilizing thesystems and methods described in U.S. Pat. No. 8,042,563, issued Oct.25, 2011, entitled “Cassette System Integrated Apparatus.”

Referring again to FIG. 55, in these exemplary embodiments of sensormanifolds that may be used in conjunction with the sensor apparatus andsensor apparatus systems described herein, the sensor manifold 4100 mayalso include printed circuit board (PCB) 4304 and a PCB cover 4305.Various embodiments may also include connector 4303 (also shown in FIGS.53 and 56B) which may be utilized to mechanically connect the cassettemanifold 4100 to the system, such as a hemodialysis system. Cassettemanifold 4100 may also utilize various methods to hold the layers ofsensor manifold 4100 together as a unit. In various embodiments, asshown in FIG. 43, connectors 4306 (also shown in FIG. 56B), which in oneembodiment is a screw, but in other embodiments may be any means forconnection, are utilized, but any means known to one of skill in theart, such as other types of screws, welds, clips, clamps, and othertypes of chemical and mechanical bonds may be utilized.

Referring now to FIG. 56A, in exemplary embodiments of the sensormanifold 4100, tube connectors, such as tube connector 4401, is utilizedto bring subject media into or remove subject media from fluid path4402. Sensing probes, such as sensing probe 4404 extending into fluidpath 4402, are incorporated into sensor manifold 4100 so as to determinevarious properties of the subject media contained in or flowing throughthe particular fluid path in the sensor manifold. In various embodimentsone sensing probe may be utilized to sense temperature and/or otherproperties of the subject media. In another embodiment, two sensingprobes may be utilized to sense temperature and/or conductivity and/orother properties of the subject media. In yet further embodiments, threeor more sensing probes may be included. In some embodiments, one or morecombination temperature and conductivity sensing probes of the typesgenerally described herein may be utilized. In other embodiments, theconductivity sensors and temperature sensor can be any conductivity ortemperature sensor in the art. In one embodiment, the conductivitysensor elements (or sensor leads) are graphite posts. In otherembodiments, the conductivity sensors elements are posts made fromstainless steel, titanium, or any other material of the type typicallyused for (or capable of being used for) conductivity measurements. Incertain embodiments, the conductivity sensors will include an electricalconnection that transmits signals from the sensor lead to a sensormechanism, controller or other device. In various embodiments, thetemperature sensor can be any of the temperature sensors commonly used(or capable of being used) to sense temperature.

Referring again to FIG. 56A, sensing probe 4404 is electricallyconnected to PCB 4405. In certain embodiments, an electricallyconductive epoxy is utilized between sensor element 4404 and PCB 4405 toensure appropriate electrical connection, although other methods knownto those of skill in the art may be used to obtain an appropriateelectrical connection between sensor element 4404 and PCB 4405. PCB 4405is shown with edge connector 4406. In various embodiments, edgeconnector 4406 may be used to transmit sensor information from cassettemanifold 4100 to the main system. Edge connector 4406 may be connectedto a media edge connector (such as media edge connector 4601 shown inFIG. 58). In various embodiments, media edge connector 4601 may beinstalled in a hemodialysis machine (not shown). In such embodiments,guide tracks 4310 and 4311 (as shown in FIG. 55) may be utilized toassist in the connection of edge connector 4406 and media edge connector4601. Various embodiments may also include connector 4303 (as shown inFIGS. 53, 55 and 56B) which may be utilized to mechanically connect thecassette manifold 4100 to the system, such as a hemodialysis system.

Referring again to FIG. 56A, air trap 4410 is shown. In certainembodiments, an air trap, such as air trap 4410, may be utilized to trapand purge air in the system. As may be best shown in FIG. 54, subjectmedia may flow through fluid path 4222 between tube connectors 4107 and4109 in sensor manifold 4100. As the flow of the subject media is slowedaround the turn in fluid path 4222 (near tube connector 4108), air maybe removed from the subject media through connector 4108.

Referring now to FIG. 56B, PCB cover 4305 is shown. PCB cover 4305 maybe connected to sensor manifold 4100 by connectors 4306. Edge connector4406 is also shown.

In accordance with certain embodiments, sensor manifold 4100 is passivewith respect to control of the fluid flow. In such embodiments, sensormanifold 4100 does not contain valves or pumping mechanisms to controlthe flow of the subject media. In such embodiments, the flow of thesubject media may be controlled by fluid control apparatus external tosensor manifold 4100. In other embodiments, the sensor manifold mayinclude one or more mechanical valves, pneumatic valves or other type ofvalve generally used by those of skill in the art. In such embodiments,the sensor manifold may include one or more pumping mechanisms,including pneumatic pumping mechanisms, mechanical pumping mechanisms,or other type of pumping mechanisms generally used by those of skill inthe art. Examples of such valves and pumping mechanisms may include thevalves and pumping mechanisms described in U.S. Pat. No. 8,273,680,issued Sep. 25, 2012, entitled “Pumping Cassette”; or U.S. Pat. No.8,042,563, issued Oct. 25, 2011, entitled “Cassette System IntegratedApparatus.”

Referring now to FIG. 57, tube connector 4401 is shown in base 4301. Topplate 4302 is shown, along with connector 4303. Sensing probes, such assensing probe 4501, extend through top plate 4302 into fluid path 4503.Sensing probe 4501 may be various types of sensors, including theembodiments of sensing probes generally discussed herein.

The sensing probes, such as sensing probe 4501, may be all the same, maybe individually selected from various sensors based on the type offunction to be performed, or the same probe may be individually modifiedbased on the type of function to be performed. Similarly, theconfiguration of the fluid paths, such as the length of the fluid pathand the shape of the fluid path, may be selected based on the functionto be performed. By way of example, to detect the temperature of thesubject media in a fluid path, a temperature sensor, such as athermistor, may be used. Again, by way of example, to measure theconductivity of the subject media, one sensing probe configured tomeasure temperature and conductivity, and one sensing probe configuredonly to measure conductivity may be utilized. In other embodiments, twoor more sensing probes configured to measure both temperature andconductivity may be utilized. In various embodiments of suchconfigurations, by way of example, the second temperature sensor may bepresent but not utilized in normal operation, or the second temperaturemay be utilized for redundant temperature measurements, or the or thesecond temperature may be utilized for redundant temperaturemeasurements.

Referring again to FIG. 57, PCB 4502 is shown with electrical connection4503. As further shown in FIG. 58, PCB 4602 is shown with electricalconnection 4603 for connection to a sensing probe (shown as 4501 in FIG.45). PCB 4602 also contains opening 4604 for attachment to top plate(shown as 4305 in FIG. 57). In certain embodiments, electricalconnection 4603 is mounted onto, or manufactured with, PCB 4602 with airgap 4606. In such embodiments, air gap 4606 may be utilized to provideprotection to the electrical connection between sensing probe 4501 andPCB 4602 by allowing shrinking and expansion of the various componentsof sensor manifold 4100 with lesser impact to PCB 4602.

Referring again to FIG. 58, PCB 4602 is also shown with edge connector4605. As described herein, edge connector 4605 may interface with edgeconnector receiver 4601, which may be connected to the system, such asthe hemodialysis system, to which sensor manifold 4100 interfaces.

Various embodiments of exemplary sensor manifold 4100 shown in FIG.53-58 may be utilized in conjunction with hemodialysis systems andmethods described in U.S. Pat. No. 8,273,049, issued Sep. 25, 2012,2007, entitled “Pumping Cassette”; or U.S. Pat. No. 8,042,563, issuedOct. 25, 2011, entitled “Cassette System Integrated Apparatus.” Incertain embodiments, sensor manifold 4100 contains all of thetemperature and conductivity sensors shown in FIG. 59. FIG. 59 depicts afluid schematic in accordance with one embodiment of the inventionsdescribed in the patent applications reference above.

By way of example, in various embodiments, the temperature andconductivity of the subject media at position 4701 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media flows into tube connector 4105 (as shown in FIG. 53)through fluid path 4220 (as shown in FIG. 54) and exits at tubeconnector 4106 (as shown in FIG. 53). The conductivity of the subjectmedia is measured by two sensing probes (not shown) extending into fluidpath 4220, at least one of which has been configured to include atemperature sensing element, such as a thermistor. The conductivitymeasurement or the temperature measurement of the subject media may beutilized to determine and/or correlate a variety of information ofutility to the hemodialysis system. For example, in various embodimentsat position 4701 in FIG. 59, the subject media may be comprised of waterto which a bicarbonate-based solution has been added. Conductivity ofthe subject media at position 4701 may be utilized to determine if theappropriate amount of the bicarbonate based solution has been addedprior to position 4701. In certain embodiments, if the conductivitymeasurement deviates from a predetermined range or deviates from apredetermined measurement by more than a predetermined amount, then thesubject media may not contain the appropriate concentration of thebicarbonate based solution. In such instances, in certain embodiments,the hemodialysis system may be alerted.

Again, by way of example, in various embodiments, the conductivity ofthe subject media at position 4702 as shown in FIG. 59 may be determinedutilizing sensor manifold 4100. In such embodiments, subject media flowsinto tube connector 4112 (as shown in FIG. 41) through fluid path 4221(as shown in FIG. 54) and exits at tube connector 4113 (as shown in FIG.53). The conductivity of the subject media is measured by two sensingprobes (not shown) extending into fluid path 4221, at least one of whichhas been configured to include a temperature sensing element, such as athermistor. The conductivity measurement or the temperature measurementof the subject media may be utilized to determine and/or correlate avariety of information of utility to the hemodialysis system. Forexample, in various embodiments at position 4702 in FIG. 59, the subjectmedia may be comprised of water to which a bicarbonate-based solutionand then an acid based solution has been added. Conductivity of thesubject media at position 4702 may be utilized to determine if theappropriate amount of the acid based solution (and the bicarbonate basedsolution in a previous step) has been added prior to position 4702. Incertain embodiments, if the conductivity measurement deviates from apredetermined range or deviates from a predetermined measurement by morethan a predetermined amount, then the subject media may not contain theappropriate concentration of the acid based solution and the bicarbonatebased solution. In such instances, in certain embodiments, thehemodialysis system may be alerted.

By way of further example, in various embodiments, the temperature andconductivity of the subject media at position 4703 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media may flow into or out of tube connector 4107 (as shown inFIG. 53) through fluid path 4222 (as shown in FIG. 54) and may flow intoor out of tube connector 4109 (as shown in FIG. 53). As describedherein, air may be removed from the subject media as it moves past theturn in fluid path 4222. In such instances, a portion of the subjectmedia may be removed through tube connector 4108 to the drain, bringingwith it air from the air trap. The conductivity of the subject media ismeasured by two sensing probes (not shown) extending into fluid path4222, at least one of which has been configured to include a temperaturesensing element, such as a thermistor. The conductivity measurement orthe temperature measurement of the subject media may be utilized todetermine and/or correlate a variety of information of utility to thehemodialysis system. For example, in various embodiments, theconductivity measurement at position 4703 in FIG. 59 may be utilized tocorrelate to the clearance of the dialyzer. In such instances, incertain embodiments, this information may then be sent to thehemodialysis system.

Again, by way of further example, in various embodiments, thetemperature of the subject media at position 4704 as shown in FIG. 59may be determined utilizing sensor manifold 4100. In such embodiments,subject media flows into tube connector 4103 (as shown in FIG. 53)through fluid path 4223 (as shown in FIG. 54) and exits at tubeconnector 4104 (as shown in FIG. 53). The temperature of the subjectmedia is measured by one or more sensing probes (not shown) extendinginto fluid path 4223. The temperature measurement of the subject mediaat position 4704 may be utilized to determine and/or correlate a varietyof information of utility to the hemodialysis system. For example, invarious embodiments at position 4704 in FIG. 59, the temperature of thesubject media is determined down stream of a heating apparatus 4706. Ifthe temperature deviates from a predetermined range or deviates from apredetermined measurement by more than a predetermined amount, then thehemodialysis system may be alerted. For example in certain embodiments,the subject media may be re-circulated through the heating apparatus4706 until the temperature of the subject media is within apredetermined range.

Again, by way of further example, in various embodiments, thetemperature and conductivity of the subject media at position 4705 asshown in FIG. 59 may be determined utilizing sensor manifold 4100. Insuch embodiments, subject media flows into tube connector 4110 (as shownin FIG. 53) through fluid path 4224 (as shown in FIG. 54) and exits attube connector 4111 (as shown in FIG. 53). The conductivity of thesubject media is measured by two sensing probes (not shown) extendinginto fluid path 4224, at least one of which has been configured toinclude a temperature sensing element, such as a thermistor. Theconductivity measurement or the temperature measurement of the subjectmedia may be utilized to determine and/or correlate a variety ofinformation of utility to the hemodialysis system. For example, thetemperature and conductivity measurement at position 4705 may be used asa further safety check to determine if the temperature, conductivity,and, by correlation, the composition of, the subject media is withinacceptable ranges prior to the subject media reaching the dialyzer 4707and, thus, the patient. In certain embodiments, if the temperatureand/or conductivity measurement deviates from a predetermined range ordeviates from a predetermined measurement by more than a predeterminedamount, then the hemodialysis system may be alerted.

For the various embodiments described herein, the cassette may be madeof any material, including plastic and metal. The plastic may beflexible plastic, rigid plastic, semi-flexible plastic, semi-rigidplastic, or a combination of any of these. In some of these embodimentsthe cassette includes one or more thermal wells. In some embodiments oneor more sensing probes and/or one or more other devices for transferringinformation regarding one or more characteristics of such subject mediaare in direct contact with the subject media. In some embodiments, thecassette is designed to hold fluid having a flow rate or pressure. Inother embodiments, one or more compartments of the cassette is designedto hold mostly stagnant media or media held in the conduit even if themedia has flow.

In some embodiments, the sensor apparatus may be used based on a need toseparate the subject media from the sensing probe. However, in otherembodiments, the sensing probe is used for temperature, conductivity,and/or other sensing directly with subject media.

Another aspect of the invention is generally directed to methods andoperations of the systems as discussed herein. For instance, ahemodialysis system may be primed, flow-balanced, emptied, purged withair, disinfected, or the like.

One set of embodiments is generally directed to priming of the systemwith a fluid. The fluid to be primed is first directed to a dialysatetank (e.g. dialysate tank 169). Ultrafilter 73 is then first primed bypushing fluid from dialysate tank 169 to ultrafilter 73, and caused toexit line 731 through waste line 39 to the drain, as is shown by theheavy black lines in FIG. 17A. Any air present in ultrafilter 73naturally rises to the priming port and is flushed to the drain.

Next, as is shown in FIG. 17B, the balancing circuit and pump 159 of thedirecting circuit are primed by pushing fluid through the ultrafilter73, through the balancing circuit, and out to the drain. Pump 159 isprimed by running fluid forwards (through the ultrafilter to the drain).Air entering dialyzer 14 bubbles to the top of the dialyzer and leavesthrough the dialyzer exit to the drain.

Next, the blood flow pump and tubing are primed by circulating fluidthrough the blood flow circuit and the air trap back to the directingcircuit via conduit 67. As can be seen in FIG. 17C, fluid passes throughthe ultrafilter and dialyzer, forcing flow through the air trap and downthe drain. The air trap traps air circulating in the blood flow circuitand sends it to the drain. Priming can be stopped when the air sensorsstop detecting air (and some additional fluid has been passed throughthe system, as a safety margin).

Another set of embodiments is directed to adding air to the system,e.g., to empty the system of various fluids. For example, in oneoperation the dialysate tank is emptied. Vent 226 on dialysate tank 169is opened, and pump 159 is used to pump fluid from the dialysate tank tothe drain until air is detected in pump 159 (discussed below). This isshown in FIG. 19.

Air may also be pumped into the balancing circuit in certainembodiments. This is shown in FIG. 20. Vent 226 on dialysate 16 isopened so that air may enter the dialysate tank. Pump 159 is used topump air through the outside of ultrafilter 73. This air pressuredisplaces fluid outside the ultrafilter to the inside, then it flowsthrough the dialyzer and down the drain. During this operation, pump 159and the outside of the ultrafilter will fill with air.

In addition, air can be drawn in through the anticoagulant pump 80 intothe blood flow circuit, as is shown in FIG. 21A. The air is firstbrought into pod pumps 23 (FIG. 21A), then may be directed from the podpumps to the arterial line 203 and down the drain (FIG. 21B), or to thevenous line 204 (through dialyzer 14) and down the drain (FIG. 21C).

In one set of embodiments, integrity tests are conducted. As theultrafilter and the dialyzer may be constructed with membrane materialthat will not readily pass air when wet, an integrity test may beconducted by priming the filter with water, then applying pressurizedair to one side of the filter. In one embodiment, an air outlet isincluded on one of the blood flow pumps and thus, the pumping chambermay be used to pump air for use in the integrity test. This embodimentuses the advantage of a larger pump. The air pressure pushes all of thewater through the filter, and the air flow stops once the water has beendisplaced. However, if the air flow continues, the membrane is rupturedand must be replaced. Accordingly, the system is primed with water.First, the mixing circuit is primed first to eliminate air prior to thedialysate tank. Then the outside of the ultrafilter is primed next, asthe ultrafilter will not pass water to the balancing circuit until theoutside is primed. The balancing circuit and the dialyzer are primednext. Finally, water is pushed across the dialyzer to prime the bloodflow circuit.

The mixing circuit is primed by first pushing water with pump 183,through line 281 and bicarbonate source 28, then through each of thepumps and through line 186 to dialysate tank 169. Dialysate tank 169 isvented so air that is pushed through bubbles to the top and leavesthrough vent 226. Once air has been primed out of dialysate tank 169,the tank is filled with water, then the priming flow continues from thedialysate tank through ultrafilter 73 to the drain. This can be seen inFIG. 22A. Water is then primed as previously discussed (see FIG. 17).Next, the blood flow pod pumps 23 are filled with water from dialysatetank 169, as is shown in FIG. 22B, while balancing pumps 15 are emptied,as is shown in FIG. 22C.

The test is conducted by using the blood flow pump to push each chamberof water across dialyzer 14 to balancing pump chambers 15, which startempty (FIG. 22C) and are vented to the atmosphere so that they arepresent at atmospheric pressure on the dialysate side of dialyzer 14.See FIG. 22D. Each of the blood flow circuit chambers delivers using aspecific pressure and the end-of-stroke is determined to determine theflow rate.

Another integrity test is the ultrafilter flow test. In this test, thedialysate tank is filled with water, the ultrafilter is primed bypumping water from the dialysate tank through the ultrafilter and outline 731, and water is pumped through the ultrafilter, controlling flowrate, monitoring the delivery pressure required to maintain flow.

Another set of embodiments are directed to disinfection and rinsing ofthe system. This process removes any material which may have accumulatedduring therapy, and kills any active pathogens. Typically, heat is used,although in some cases, a disinfectant may be added. Water is maintainedusing the dialysate tank and replenished as necessary as water isdischarged.

A recirculating flow path is shown in FIG. 23. The flow along this pathis essentially continuous, and uses conduits 67 to connect the bloodflow circuit with the directing circuit. The main flow path is heatedusing heater 72, which is used to increase the water temperature withinthe recirculating flow path, e.g., to a temperature that can kill anyactive pathogens that may be present. Most of the water is recirculated,although some is diverted to drain. Note that lines 48 and 731 are keptopen in this example to ensure that these lines are properlydisinfected. In addition, the flow paths through ultrafilter 73 can beperiodically selected to purge air from the ultrafilter, and/or toprovide recirculating flow through this path. Temperature sensors (e.g.,sensors 251 and 252) can be used to ensure that proper temperatures aremet. Non-limiting examples of such sensors can be seen in U.S. Pat. No.8,491,184, issued Jul. 23, 2013, entitled “Sensor Apparatus Systems,Devices and Methods,” incorporated herein by reference.

In one set of embodiments, the system is primed with dialysate asfollows. In this operation, pod pump 280 is filled with water (FIG.24A), and then water is pushed backwards through pump 183 to expel airfrom the top of bicarbonate source 28. The air is collected in pod pump282. See FIG. 24B. Next, the air in pod pump 282 is expelled through podpump 280 and line 186 to dialysate tank 169. Vent 226 in dialysate tank169 is opened so that the air can leave the system (FIG. 24C). Inaddition, acid may be pumped in from acid source 29. Bicarbonateconcentrate from bicarbonate source 28 and water are then mixed. Pump183 is used to provide water pressure sufficient to fill bicarbonatesource 28 with water, as is shown in FIG. 24D.

The acid and bicarbonate solutions (and sodium chloride solution, if aseparate sodium chloride source is present) are then metered withincoming water to prepare the dialysate. Sensors 178 and 179 are used toensure that the partial mixtures of each ingredient with water iscorrect. Dialysate that does not meet specification is emptied to thedrain, while good dialysate is pumped into dialysate tank 14.

In another set of embodiments, the anticoagulant pump is primed. Primingthe pump removes air from the heparin pump and the flow path, andensures that the pressure in the anticoagulant vial is acceptable. Theanticoagulant pump can be designed such that air in the pump chamberflows up into the vial. The test is performed by closing all of theanticoagulant pump fluid valves, measuring the external volume, chargingthe FMS chamber with vacuum, opening valves to draw from the vial intothe pumping chamber, measuring the external volume (again), charging theFMS chamber with pressure, opening the valves to push fluid back intothe vial, and then measuring the external volume (again). Changes inexternal volume that result from fluid flow should correspond to theknown volume of the pumping chamber. If the pumping chamber cannot fillfrom the vial, then the pressure in the vial is too low and air must bepumped in. Conversely, if the pumping chamber cannot empty into thevial, then the pressure in the vial is too high and some of theanticoagulant must be pumped out of the vial. Anticoagulant pumped outof the vial during these tests can be discarded, e.g., through thedrain.

In yet another set of embodiments, the system is rinsed with dialysatewhile the patient is not connected. This can be performed before orafter treatment. Prior to treatment, dialysate may be moved and aportion sent to the drain to avoid accumulating sterilant in thedialysate. After treatment, this operation rinses the blood path withdialysate to push any residual blood to the drain. The flow paths usedin this operation are similar to the flow paths used with water, asdiscussed above.

Acid concentrate may be pumped out of the mixing chamber. Pump 184 isactivated so that pod pump 280 can draw out acid from pump 184 and acidsource 29, to be mixed in line 186 and sent to the drain. Similarly,bicarbonate may be pumped out of the mixing chamber as is shown in FIG.25. Pump 183 is used to draw water from bicarbonate source 28, then podpump 280 is used to pass the water into line 186 to the drain.

In still another set of embodiments, dialysate prime is removed from theblood flow circuit, to avoid giving the patient the priming fluid. FIGS.26A and 26B show fluid leaving each of the balancing pump chambers andbeing expelled to the drain. Next, the dialysate side of dialyzer 14 isclosed, while blood is drawn into the blood flow path from the patient(FIG. 26C). The patient connections are then occluded while the bloodflow pump chambers 23 push the priming fluid across the dialyzer to thebalancing circuit (FIGS. 26D and 26E). This fluid is then pushed todrain, as previously discussed. This operation can be repeated asnecessary until sufficient priming fluid has been removed. Afterwards,the balancing pumps are then refilled with fresh dialysate, keeping thepatient connections occluded, as is shown in FIG. 26F.

In yet another set of embodiments, a bolus of anticoagulant may bedelivered to the patient. Initially, a bolus of anticoagulant is pumpedfrom the vial (or other anticoagulant supply) to one chamber of pump 13,as is shown in FIG. 27A. The anticoagulant pump alternates betweenpumping air into the vial and pumping anticoagulant out of the vial,thereby keeping the pressure relatively constant. The remaining volumeis then filled with dialysate (FIG. 27B). The combined fluids are thendelivered to the patient down arterial line 203, as shown in FIG. 27B.In some cases, the same pump chamber may be refilled with dialysateagain (see FIG. 27B), and that volume delivered to the patient also, toensure that all of the anticoagulant has been properly delivered.

In still another set of embodiments, the system may perform push-pullhemodiafiltration. In such cases, blood flow pump 13 and balancing pumps15 can be synchronized to pass fluid back and forth across the dialyzer.In hemodiafiltration, hydrostatic pressure is used to drive water andsolute across the membrane of the dialyzer from the blood flow circuitto the balancing circuit, where it is drained. Without wishing to bebound by any theory, it is believed that larger solutes are more readilytransported to the used dialysate due to the convective forces inhemodiafiltration.

In one set of embodiments, solution infusion may be used to deliveryfluid to the patient. As is shown in FIG. 28, pump 159 in the directingcircuit is used to push fluid across dialyzer 14 into the blood flowcircuit, which thus causes delivery of fluid (e.g., dialysate) to thepatient.

According to another set of embodiments, after repeated use, thedialyzer can lose its efficiency or even the ability to function at allas a result of compounds adhering to and building up on the membranewalls in the dialyzer. Any standard measure of dialyzer clearancedetermination may be used. However, one method of measuring how muchbuild-up has accumulated in the dialyzer, i.e., how much the dialyzer'sclearance has deteriorated, a gas is urged into the blood side of thedialyzer, while a liquid is held on the dialysate side of the dialyzer.By measuring the volume of gas in the dialyzer, the clearance of thedialyzer may be calculated based on the volume of gas measured in thedialyzer.

Alternatively, in other embodiments, because of the pneumatic aspects ofthe present system, clearance may be determined as follows. By applyinga pressure differential along the dialyzer and measuring the flow rateof the dialyzer, the clearance of the dialyzer may then becorrelated/determined or calculated, based on the pressure differentialand the flow rate. For example, based on a known set of correlations orpre-programmed standards including a correlation table or mathematicalrelationship. For example, although a look-up table may be used, or adetermined mathematical relationship may also be used.

The dialyzer's clearance can also be measured using a conductivity probein the blood tube plug-back recirculation path. After treatment thepatient connects the blood tubes back into the disinfection ports. Thefluid in the blood tubes and dialyzer may be recirculated through thesedisinfection port connections, and the conductivity of this solution maybe measured as it passes through the conductivity measurement cell inthis recirculation path.

To measure the dialyzer clearance, pure water may be circulated throughthe dialysate path and the conductivity of the fluid flowing through theblood recirculation path is continuously monitored. The pure water takesions from the solution in the blood flow circuit recirculation path at arate which is proportional to the clearance of the dialyzer. Theclearance of the dialyzer may be determined by measuring the rate atwhich the conductivity of the solution in the blood flow circuitrecirculation path changes.

The dialyzer's clearance can be measured by circulating pure water onone side and dialysate on the other, and measuring the amount of fluidpassing through the dialyzer using conductivity.

In one set of embodiments, in case of a power failure, it may bedesirable to return as much blood to the patient as possible. Since oneembodiment of the hemodialysis system uses compressed gas to actuatevarious pumps and valves used in the system, a further embodiment takesadvantage of this compressed gas to use it in case of power failure toreturn blood in the system to the patient. In accordance with thisprocedure and referring to FIG. 29A, dialysate is pushed across thedialyzer 14, rinsing blood residing blood flow circuit 10 back to thepatient. Compressed air is used to push dialysate across the dialyzer14. A valve 77 releases the compressed air to initiate this function.This method may be used in situations where electrical power loss orsome other failure prevents the dialysis machine from rinsing back thepatient's blood using the method normally employed at the end oftreatment.

As compressed air is used to increase the pressure on the dialysate sideof the dialyzer 14 and force dialysate through the dialyzer to the bloodside, thereby pushing the patient's blood back to the patient, thepatient, or an assistant, monitors the process and clamps the tubesbetween the blood flow circuit and the patient once adequate rinse backhas been achieved.

In one embodiment, a reservoir 70 is incorporated into the hemodialysissystem and is filled with compressed air prior to initiating treatment.This reservoir 70 is connected to the dialysate circuit 20 through amanually actuated valve 77. When the treatment is finished or aborted,this valve 77 is opened by the patient or an assistant to initiate therinse-back process. The membrane of the dialyzer 14 allows dialysate topass through, but not air. The compressed air displaces dialysate untilthe patient tubes are clamped, or the dialysate side of the dialyzer isfilled with air.

In another embodiment, a reservoir containing compressed air is providedas an accessory to the dialysis machine. If the treatment is terminatedearly due to a power failure or system failure of the dialysis machine,this reservoir may be attached to the dialysate circuit on the machineto initiate the rinse-back process. As in the previous embodiment, therinse-back process is terminated when the patient tubes are clamped, orthe dialysate side of the dialyzer is filled with air.

In yet another embodiment shown in FIG. 29B, an air reservoir 70 isincorporated into the system and attached to a fluid reservoir 75 with aflexible diaphragm 76 separating the air from the dialysate fluid. Inthis case, the compressed air pushes the diaphragm 76 to increase thepressure in the dialysate circuit 20 rather than having the compressedair enter the dialysate circuit. The volume of the dialysate that isavailable to be displaced is determined by the volume of the fluidchamber 75. The rinse-back process is terminated when the patient tubesare clamped, or when all of the fluid is expelled and the diaphragm 76bottoms out against the wall of the fluid chamber 75.

In any of these embodiments, the operation of the systems or methods maybe tested periodically between treatments by running a program on thedialysate machine. During the test the user interface prompts the userto actuate the rinse-back process, and the machine monitors the pressurein the dialysate circuit to ensure successful operation.

In the systems depicted in FIGS. 29A and 29B, blood is drawn from thepatient by the blood flow pump 13, pushed through the dialyzer 14 andreturned to the patient. These components and the tubing that connectsthem together make up the blood flow circuit 10. The blood contained inthe blood flow circuit 10 should be returned to the patient when thetreatment is finished or aborted.

The dialysate solution is drawn from the dialysate tank 169 by thedialysate pump 159, and passed through the heater 72 to warm thesolution to body temperature. The dialysate then flows through theultrafilter 73 which removes any pathogens and pyrogens which may be inthe dialysate solution. The dialysate solution then flows through thedialyzer to perform the therapy and back to the dialysate tank.

The bypass valves 74 may be used to isolate the dialyzer 14 from therest of the dialysate circuit 20. To isolate the dialyzer 14, the twovalves connecting the dialysate circuit 20 to the dialyzer are closed,and the one shunting dialysate around the dialyzer is opened.

This rinse-back procedure may be used whether or not the dialyzer 14 isisolated and is used when the treatment is ended or aborted. Thedialysate machine is turned off or deactivated so the pumps are notrunning. When the patient is ready for rinse-back, air valve 77 isopened by the patient or an assistant. The air in the compressed airreservoir 70 flows toward the dialysate circuit 20, increasing thepressure on the dialysate side of the dialyzer 14. This increase inpressure may be achieved by allowing the air to enter the dialysatecircuit directly, as shown in FIG. 29A or indirectly by pushing on thediaphragm 76 shown in FIG. 29B.

The air pressure on the dialysate side of the dialyzer forces somedialysate solution through the dialyzer 14 into the blood flow circuit.This dialysate solution displaces the blood, rinsing the blood back tothe patient. The patient or an assistant can observe the rinse processby looking at the dialyzer 14 and the blood tubes. The dialysatesolution starts in the dialyzer, displacing the blood and making itappear much clearer. This clearer solution progresses from the dialyzertoward the patient. When it reaches the patient the blood tube clamps 71are used to pinch the tubing to terminate the rinse-back process. If oneline rinses back sooner than the other the quicker line may be clampedfirst and the slower line may be clamped later.

Once the rinse-back is completed and the blood lines are clamped thepatient may be disconnected from the dialysis machine.

The implementation of one embodiment of the system and method is shownin FIG. 29A takes advantage of the hydrophilic nature of the materialused to make the tiny tubes in the dialyzer 14. When this material iswet, the dialysate solution can pass through but air cannot. Where theembodiment shown in FIG. 29A is implemented, air may enter the dialyzer14 but it will not pass across to the blood flow circuit 10.

In either implementation, the volume of dialysate that may be passedthrough the dialyzer 14 is limited. This limitation is imposed by thesize of the compressed air reservoir 70, the volume of dialysatesolution contained in the dialyzer 14 and in the case of theimplementation shown in FIG. 7B the size of fluid reservoir 75. It isadvantageous to limit the volume of dialysate that may be pushed acrossthe dialyzer because giving too much extra fluid to the patientcounteracts the therapeutic benefit of removing fluid during thetherapy.

Another aspect of the invention is generally directed to a userinterface for the system. The user interface may be operated by anindividual, such as the patient, a family member, assistant,professional care provider, or service technician, to input options,such as treatment options, and to receive information, such asinformation about the treatment protocol, treatment status, machinestatus/condition, and/or the patient condition. The user interface maybe mounted on the treatment device and controlled by one or moreprocessors in the treatment device. In another embodiment, the userinterface may be a remote device that may receive, transmit, or transmitand receive data or commands related to the treatment protocol,treatment status, and/or patient condition, etc. The remote device maybe connected to the treatment device by any suitable technique,including optical and/or electronic wires, wireless communicationutilizing Bluetooth, RF frequencies, optical frequencies, IRfrequencies, ultrasonic frequencies, magnetic effects, or the like, totransmit and/or receive data and/or commands from or to the treatmentdevice. In some cases, an indication device may be used, which canindicate when data and/or a command has been received by the treatmentdevice or the remote device. The remote device may include input devicessuch as a keyboard, touch screen, capacitive input device, or the liketo input data and/or commands to the treatment device.

In some embodiments, one or more processors of the treatment device mayhave a unique identification code and the remote device may include thecapability to read and learn the unique identification code of thetreatment. Alternatively, the user can program in the uniqueidentification code. The treatment device and the remote device may usea unique identification code to substantially avoid interference withother receivers, including other treatment device.

In one set of embodiments, the treatment device may have one or moreprocessors that are connected to a web-enabled server and the userinterface device may be run on this web-enabled server. In oneembodiment, the device uses an external CPU (e.g., a GUI, graphical userinterface) to communicate via Internet protocol to the embedded webserver in or connected to the treatment device. The web page may beserved up inside the device and the GUI may communication directly via802.11b or other such weird or wireless Ethernet equivalent. The GUI maybe operated by an individual, such as the patient, a family member,assistant, professional care provider, or service technician, to inputoptions, such as treatment options, and to receive information, such asinformation about the treatment protocol, treatment status, machinestatus/condition, and/or the patient condition.

In another embodiment, the embedded web server in or connected to thetreatment device may communicate to an appropriate site on the Internet.The Internet site may require a password or other user identification toaccess the site. In another embodiment, the user may have access todifferent information depending on the type of user and the accessprovider. For example, a patient or professional caregiver may have fullaccess to patient treatment options and patient information, while afamily member may be given access to certain patient information, suchas the status and duration remaining for a given treatment or frequencyof treatments. The service technician, dialysis center, or treatmentdevice provider may access other information for troubleshooting,preventive maintenance, clinical trials, and the like. Use of theweb-enabled server may allow more than one individual to access patientinformation at the same time for a variety of purposes.

The use of a remote device, e.g., via wired or wireless communication,Internet protocol, or through an Internet site utilizing a web enableserver, could allow a dialysis center to more effectively monitor eachpatient and/or more efficiently monitor a larger number of patientssimultaneously. In some embodiments, the remote device can serve as anocturnal monitor or nocturnal remote alert to monitor the patientduring nocturnal dialysis treatment and to provide an alarm if thepatient's condition does not meet certain parameters. In some cases, theremote device may be used to provide alarms to the patient, a familymember, assistant, professional care provider, or service technician.These alarms could alert an individual to certain conditions such as,but not limited to, a fluid leak, an occlusion, temperature outsidenormal parameters, and the like. These alarms may be audible alarms,visual alarms, and/or vibratory alarms.

The following are each incorporated herein by reference in theirentireties: U.S. Provisional Patent Application Ser. No. 60/903,582,filed Feb. 27, 2007, entitled “Hemodialysis System and Methods”; U.S.Provisional Patent Application Ser. No. 60/904,024, filed Feb. 27, 2007,entitled “Hemodialysis System and Methods”; U.S. Patent ApplicationPublication No. US 2008-0058697, published Mar. 6, 2008, entitled “HeatExchange Systems, Devices and Methods”; U.S. Pat. No. 8,292,594, issuedOct. 23, 2012 and entitled “Fluid Pumping Systems, Devices and Methods”;U.S. Pat. No. 7,794,141, issued Sep. 14, 2010, entitled “Thermal andConductivity Sensing Systems, Devices and Methods”; U.S. Pat. No.8,273,049, issued Oct. 25, 2012, entitled “Pumping Cassette”; U.S. Pat.No. 8,317,492, issued Nov. 27, 2012, entitled “Pumping Cassette”; U.S.Patent Application Publication No. US 2008-0253911, published Oct. 16,2008, entitled “Pumping Cassette”; U.S. Patent Publication No. US2008-0253912, filed Oct. 16, 2008, entitled “Pumping Cassette”; and U.S.Pat. No. 7,967,803, issued Jun. 28, 2011, entitled “Cassette SystemIntegrated Apparatus.” In addition, the following are incorporated byreference in their entireties: U.S. Pat. No. 4,808,161, issued Feb. 28,1989, entitled “Pressure-Measurement Flow Control System”; U.S. Pat. No.4,826,482, issued May 2, 1989, entitled “Enhanced Pressure MeasurementFlow Control System”; U.S. Pat. No. 4,976,162, issued Dec. 11, 1990,entitled “Enhanced Pressure Measurement Flow Control System”; U.S. Pat.No. 5,088,515, issued Feb. 18, 1992, entitled “Valve System withRemovable Fluid Interface”; and U.S. Pat. No. 5,350,357, issued Sep. 27,1994, entitled “Peritoneal Dialysis Systems Employing a LiquidDistribution and Pumping Cassette that Emulates Gravity Flow.” Alsoincorporated herein by reference are U.S. Pat. No. 8,491,184, issuedJul. 23, 2013, entitled “Sensor Apparatus Systems, Devices and Methods,”incorporated herein by reference, and U.S. Pat. No. 8,042,563, issuedOct. 25, 2011, entitled “Cassette System Integrated Apparatus,”incorporated herein by reference.

While several embodiments of the present invention have been describedand illustrated herein, those of ordinary skill in the art will readilyenvision a variety of other means and/or structures for performing thefunctions and/or obtaining the results and/or one or more of theadvantages described herein, and each of such variations and/ormodifications is deemed to be within the scope of the present invention.More generally, those skilled in the art will readily appreciate thatall parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the teachings of thepresent invention is/are used. Those skilled in the art will recognize,or be able to ascertain using no more than routine experimentation, manyequivalents to the specific embodiments of the invention describedherein. It is, therefore, to be understood that the foregoingembodiments are presented by way of example only and that, within thescope of the appended claims and equivalents thereto, the invention maybe practiced otherwise than as specifically described and claimed. Thepresent invention is directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe scope of the present invention.

All definitions, as defined and used herein, should be understood tocontrol over dictionary definitions, definitions in documentsincorporated by reference, and/or ordinary meanings of the definedterms.

The indefinite articles “a” and “an,” as used herein in thespecification and in the claims, unless clearly indicated to thecontrary, should be understood to mean “at least one.”

The phrase “and/or,” as used herein in the specification and in theclaims, should be understood to mean “either or both” of the elements soconjoined, i.e., elements that are conjunctively present in some casesand disjunctively present in other cases. Multiple elements listed with“and/or” should be construed in the same fashion, i.e., “one or more” ofthe elements so conjoined. Other elements may optionally be presentother than the elements specifically identified by the “and/or” clause,whether related or unrelated to those elements specifically identified.Thus, as a non-limiting example, a reference to “A and/or B”, when usedin conjunction with open-ended language such as “comprising” can refer,in one embodiment, to A only (optionally including elements other thanB); in another embodiment, to B only (optionally including elementsother than A); in yet another embodiment, to both A and B (optionallyincluding other elements); etc.

As used herein in the specification and in the claims, “or” should beunderstood to have the same meaning as “and/or” as defined above. Forexample, when separating items in a list, “or” or “and/or” shall beinterpreted as being inclusive, i.e., the inclusion of at least one, butalso including more than one, of a number or list of elements, and,optionally, additional unlisted items. Only terms clearly indicated tothe contrary, such as “only one of” or “exactly one of,” or, when usedin the claims, “consisting of,” will refer to the inclusion of exactlyone element of a number or list of elements. In general, the term “or”as used herein shall only be interpreted as indicating exclusivealternatives (i.e. “one or the other but not both”) when preceded byterms of exclusivity, such as “either,” “one of,” “only one of,” or“exactly one of.” “Consisting essentially of,” when used in the claims,shall have its ordinary meaning as used in the field of patent law.

As used herein in the specification and in the claims, the phrase “atleast one,” in reference to a list of one or more elements, should beunderstood to mean at least one element selected from any one or more ofthe elements in the list of elements, but not necessarily including atleast one of each and every element specifically listed within the listof elements and not excluding any combinations of elements in the listof elements. This definition also allows that elements may optionally bepresent other than the elements specifically identified within the listof elements to which the phrase “at least one” refers, whether relatedor unrelated to those elements specifically identified. Thus, as anon-limiting example, “at least one of A and B” (or, equivalently, “atleast one of A or B,” or, equivalently “at least one of A and/or B”) canrefer, in one embodiment, to at least one, optionally including morethan one, A, with no B present (and optionally including elements otherthan B); in another embodiment, to at least one, optionally includingmore than one, B, with no A present (and optionally including elementsother than A); in yet another embodiment, to at least one, optionallyincluding more than one, A, and at least one, optionally including morethan one, B (and optionally including other elements); etc.

It should also be understood that, unless clearly indicated to thecontrary, in any methods claimed herein that include more than one stepor act, the order of the steps or acts of the method is not necessarilylimited to the order in which the steps or acts of the method arerecited.

In the claims, as well as in the specification above, all transitionalphrases such as “comprising,” “including,” “carrying,” “having,”“containing,” “involving,” “holding,” “composed of,” and the like are tobe understood to be open-ended, i.e., to mean including but not limitedto. Only the transitional phrases “consisting of” and “consistingessentially of” shall be closed or semi-closed transitional phrases,respectively, as set forth in the United States Patent Office Manual ofPatent Examining Procedures, Section 2111.03.

What is claimed is:
 1. A hemodialysis system, comprising: a blood flowpath through which blood is drawn from a patient and passed through adialyzer; the blood flow path comprising a pump cassette that includesat least one pneumatically actuated diaphragm-based blood pump forpumping blood; the pump cassette including a pneumatically actuateddiaphragm-based medication pump for pumping medication into the bloodflow path; the medication pump being in valved connection with an airvent on the pump cassette; and a controller for controlling pneumaticactuation pressure delivered to the blood pump, medication pump and oneor more diaphragm-based valves that connect the blood pump, medicationpump and air vent to the blood flow path; wherein the hemodialysissystem is configured to actuate the blood pump or medication pump, andthe one or more valves to introduce air into the blood flow path andexpel liquid from the blood flow path to a drain.
 2. The hemodialysissystem of claim 1, wherein the at least one blood pump comprises a firstand a second blood pump, and wherein the hemodialysis system isconfigured to actuate the first blood pump to pump air through a venousline and a dialyzer of the blood flow path to drain, and to actuate thesecond blood pump to pump air through an arterial line of the blood flowpath to drain.
 3. The hemodialysis system of claim 1, wherein themedication pump is an anticoagulant pump.
 4. The hemodialysis system ofclaim 1, wherein the medication pump is connected to three fluid valves,the first fluid valve connected to a first flowpath in the pump cassettefor connection to a medication vial, the second fluid valve connected asecond flowpath in the pump cassette to the air vent, and the thirdfluid valve connected to a third flowpath in the pump cassette forconnection to the blood flow path.
 5. The hemodialysis system of claim4, wherein the medication pump is configured to pump medication from amedication vial to the blood flow path, and to pump air from the airvent to the medication vial.
 6. The hemodialysis system of claim 1,wherein the air vent includes an air filter.
 7. The hemodialysis systemof claim 6, wherein the air filter is a hydrophobic air filter.
 8. Ahemodialysis system, comprising: a pump cassette comprising a pair ofpneumatically actuated diaphragm-based main pumps, each said main pumphaving an inlet in valved connection with a cassette inlet, and anoutlet in valved connection with a cassette outlet; the pump cassettefurther comprising a pneumatically actuated diaphragm-based meteringpump, the metering pump having a first valved connection with an airvent on the pump cassette, a second valved connection with a medicationport of the pump cassette, and a third valved connection with the outletor inlet of the pump cassette; the pump cassette further comprising aplurality of pneumatically actuated diaphragm-based valves, said valvescomprising the valved connections of the main pumps and of the meteringpump; and a controller configured to control pneumatic pressuredelivered to the main pumps, the metering pump, and the plurality ofvalves, to actuate the metering pump to pump air from the air vent tothe inlet or outlet of the pump cassette in order to drain fluid out ofone or more fluid lines connected to the pump cassette.
 9. Thehemodialysis system of claim 8, wherein the controller is configured tocontrol pneumatic pressure delivered to the main pumps, the meteringpump and the plurality of valves, to actuate the metering pump to pumpair from the air vent to a first one of the pair of main pumps, and toactuate the first one of the pair of main pumps to pump air to the inletor outlet of the pump cassette.
 10. The hemodialysis system of claim 8,wherein the controller is configured to control pneumatic pressuredelivered to the main pumps, the metering pump and the plurality ofvalves, to actuate the metering pump to pump air from the air vent to afirst one of the pair of main pumps and to pump air from the air vent toa second one of the pair of main pumps, and to actuate the first one ofthe main pumps to pump air to the inlet of the pump cassette, and toactuate the second one of the main pumps to pump air to the outlet ofthe pump cassette.
 11. The hemodialysis system of claim 8, wherein thecontroller is configured to control pneumatic pressure delivered to themain pumps, the metering pump and the plurality of valves, to actuatethe metering pump to pump air from the air vent to the medication portof the pump cassette.
 12. The hemodialysis system of claim 11, whereinthe medication port is configured for connection to an anticoagulantcontainer, and the inlet and outlet of the pump cassette are configuredfor connection to a blood flow path of the hemodialysis system.
 13. Ahemodialysis system comprising: a pump cassette comprising: a pair ofpneumatically actuated diaphragm-based main pumps, each said main pumphaving an inlet in valved connection with a cassette inlet, and anoutlet in valved connection with a cassette outlet; a pneumaticallyactuated diaphragm-based metering pump, the metering pump having a firstvalved connection with an air vent on the pump cassette, a second valvedconnection with a medication port of the pump cassette, and a thirdvalved connection with the outlet or inlet of the pump cassette; aplurality of pneumatically actuated diaphragm-based valves, a firstvalve interposed between a first one of the pair of main pumps and thecassette inlet, a second valve interposed between a second one of thepair of main pumps and the cassette inlet, a third valve interposedbetween the first one of the pair of main pumps and the cassette outlet,a fourth valve interposed between the second one of the pair of mainpumps and the cassette outlet, a fifth valve interposed between themetering pump and the air vent, a sixth valve interposed between themetering pump and the medication port, and a seventh valve interposedbetween the metering pump and the cassette inlet or outlet; and acontroller configured to control pneumatic pressure delivered to themain pumps, the metering pump, and the first through seventh valves, toactuate the metering pump to pump air from the air vent to the inlet oroutlet of the pump cassette in order to drain fluid out of one or morefluid lines connected to the pump cassette.
 14. The hemodialysis systemof claim 13, wherein the controller is configured to control pneumaticpressure delivered to the main pumps, the metering pump and the firstthrough seventh valves, to actuate the metering pump to pump air fromthe air vent to a first one of the pair of main pumps, and to actuatethe first one of the pair of main pumps to pump air to the inlet oroutlet of the pump cassette.
 15. The hemodialysis system of claim 13,wherein the controller is configured to control pneumatic pressuredelivered to the main pumps, the metering pump and the first throughseventh valves, to actuate the metering pump to pump air from the airvent to a first one of the pair of main pumps and to pump air from theair vent to a second one of the pair of main pumps, and to actuate thefirst one of the main pumps to pump air to the inlet of the pumpcassette, and to actuate the second one of the main pumps to pump air tothe outlet of the pump cassette.
 16. The hemodialysis system of claim13, wherein the controller is configured to control pneumatic pressuredelivered to the main pumps, the metering pump and the first throughseventh valves, to actuate the metering pump to pump air from the airvent to the medication port of the pump cassette.
 17. The hemodialysissystem of claim 16, wherein the medication port is configured forconnection to an anticoagulant container, and the inlet and outlet ofthe pump cassette are configured for connection to a blood flow path ofthe hemodialysis system.